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PRACTICAL

ORGANIC CHEMISTRY
by
FREDERICK GEORGE MANN
Sc-D. (Cantab.), D.Sc. (Lond.), F.R.I.C., F.R.S.
FELLOW, T R I N I T Y COLLEGE, C A M B R I D G E ,
UNIVERSITY E M E R I T U S READER I N O R G A N I C CHEMISTRY

and
BERNARD CHARLES SAUNDERS
C.B.E., M.A., Sc.D. (Cantab.), D.Sc. (Lond.), F.R.I.C., F.R.C. Path.

LONGMAN
London and New York
LONGMAN GROUP LIMITED
London
Associated companies, branches and representatives
throughout the world

Published in the United States of America


by Longman Inc., New York

Fourth Edition © Frederick George Mann and


Bernard Charles Saunders 1960

All rights reserved. No part of this publication may be


reproduced, stored in a retrieval system, or transmitted in any
form or by any means, electronic, mechanical, photocopying,
recording, or otherwise, without the prior permission of the
Copyright owner.

First Published 1936


Second Edition 1938
New Impressions 1941,1942, 1943,I944, X946,1947, T949, *952
Third Edition 1952
New Impressions 1954, *955, I956, I957> J95<?
Fourth Edition 1960
New Impressions 1961, 1962, 1964, 1967, /970, /977
Neiv Impression with revisions 1974
New Impression KJ/5
Reprinted in paper covers, igj8

British Library Cataloguing in Publication Data


XEW IMPRESSION, 1974
The last (4th) Edition of this book appeared in 1960, and has been
followed by four New Impressions, the last in 1967. The rapid
and ceaseless changing of the presentation of organic chemistry—
both theoretical and practical—warranted an entirely new edition,
but this would have entailed a massive task, for which neither
Dr. B. C. Saunders nor I had time or opportunity to undertake.
The publishers therefore suggested that a new impression
should be prepared. This also proved a laborious task, partly
because of the many minor changes in nomenclature and—more
particularly—the presentation of names that the recommenda-
tions of the LU.P.A.C. required, and partly because all correc-
tions and additions were necessarily limited in length to the
space which the original text had occupied.
Several of my chemical colleagues have suggested that a new
edition of 'M. and S.' should now deal also with the chief
branches of modern spectroscopy. This would be an aim both
excellent and impracticable. Students have their own mono-
graphs on spectroscopy and their own teachers, whose exposition
should clarify the branches of this subject more rapidly and easily
than the printed text. An attempt to deal adequately with
spectroscopy in this volume would greatly increase its size and
probably fail in purpose—the fate of several books whose authors
have attempted this ambitious programme.
Wc are greatly indebted to Dr. D. K. C. Cooper, F.R.C.S.,
who has critically examined the section on First-Aid to ensure
that it now harmonises with modern medical practice.

F. G. Mann,
University Chemical Laboratory,
Cambridge.
March 1973.
PREFACE TO FOURTH EDITION

IN the preparation of this revised and extended edition, we have


had in mind two major factors.
First, considerably greater emphasis has been placed on semi-
micro techniques and their application to preparations, separa-
tions, analysis and physical determinations such as those of
molecular weight. We have therefore greatly expanded the
section on Manipulation on a semi-micro scale which was in the
Third Edition, and we have described many more preparations
on this scale, some independent and others as alternatives to
the larger-scale preparations which immediately precede them.
Some 40 separate preparations on the semi-micro scale are
described in detail, in addition to specific directions for the
preparation of many classes of crystalline derivatives required
for identification purposes. The equipment required for these
small-scale reactions has been selected on a realistic basis, and
care has been taken not to include the very curious pieces of
apparatus sometimes suggested as necessary for working on the
semi-micro scale.
Secondly, whilst retaining undiminished the full and clear
directions provided for students who are starting the study of
practical organic chemistry, we have extended the scope of the
work so that it covers most of the needs of students working for
an Honours or Special Degree.
To meet the needs of the advanced students, preparations
have now been included to illustrate, for example, reduction by
lithium aluminium hydride and by the Meerwein-Ponndorf-
Verley method, oxidation by selenium dioxide and by periodate,
the Michael, Hoesch, Leuckart and Doebner-Miller Reactions,
the Knorr pyrrole and the Hantzsch collidine syntheses, various
Free Radical reactions, the Pinacol-Pinacolone, Beckmann and
Arbusov Rearrangements, and the Bart and the Meyer Reactions,
together with many others.
These preparations, with those noted in the Preface to the
Third Edition, cover a considerable proportion of the standard
synthetic reactions. Most of these preparations come towards the
end of Part II (Preparations), and both elementary and advanced
students should have no difficulty in selecting the preparative
work they require.
In earlier editions, Part III (Reactions and Identification of
viii PREFACE TO FOURTH EDITION
Organic Compounds) was designed to give students a thorough
training in the general reactions of the simpler members of each
of the main classes of organic compounds, and in the methods
by which an unknown compound could be first allocated to its
class and then identified. Clearly, more advanced students will
meet a wider range of members of each class of compound, and
the final identification must usually be based on the melting-
points of crystalline derivatives. We have therefore inserted in
the account of each class a note of the types of crystalline deriva-
tives which can be most rapidly and reliably prepared, with full
experimental details. Our Tables of Melting-points of deriva-
tives, given at the end of the book, have been very considerably
extended, so that the advanced student, who, like the elementary
student, must first allocate his unknown compound to its class,
can now prepare one or more crystalline derivatives, and com-
plete the identification by reference to these tables. The pre-
paration of these crystalline derivatives gives the student a
further and very valuable exercise in semi-micro preparations.
It should be emphasised that in Sections 10-27 °f ^ai"t HI,
i.e., the sections which are each devoted to one class of com-
pound, the simpler or more common members are still clearly
specified, and their reactions discussed, so that again the less
advanced student can readily discern the range of the material
which is his immediate concern.
For the more advanced student, we have extended the section
on Quantitative Semi-micro Analysis, and we have included a
section dealing with Special Techniques in Separation and
Purification, namely Adsorption Chromatography, Paper Chro-
matography, and Ion-Exchange Processes.
The use of more complex or more costly articles of equipment,
such as catalytic hydrogenation apparatus, autoclaves, polari-
meters, ultraviolet absorption spectrometers, etc., has not been
described, because the type of such apparatus employed in different
laboratories varies considerably, and students must be taught the
use of their own laboratory equipment.
In the First Edition of this book, we included a short section
to illustrate some of the more simple or the more clearly defined
reactions which are promoted by enz\mes. It was hoped that
this section might stimulate the interest of younger chemists in
the preparative value oi such T cactioris, but organic chemists still
largely ignore this branch oi preparative work. We have now
deleted certain portions of this section, and emphasised other
portions having greater current interest.
PREFACE TO FOURTH EDITION ix
Throughout this edition the nomenclature adopted is in
general that recommended by the International Union of Pure
and Applied Chemistry, and by the Chemical Society (1959).
In the preparation of this edition, we are indebted for much
help to many of our colleagues, and in particular to Dr. P. Sykes,
Dr. F. B. Kipping, Dr. P. Maitland, Dr. J. Harley-Mason and
Dr. R. E. D. Clark. We have maintained the standard which
was self-imposed \vhen this book was first written, namely, that
all the experiments in the book had been critically examined,
and then performed either by the authors, or under their super-
vision. The heavy load of work \vhich this has involved would
have been impossible without the willing, patient, and very
considerable help of AIr. F. C. Baker and Mr. F. E. G. Smith.
F. G. M.
Cambridge, 1960 B.C.S.
PREFACE TO THIRD EDITION

FOR the production of this edition, we have made a thorough and


critical revision of the whole contents of the book, based on our
experience of its use in the laboratory and on the general advance
in organic chemical practice. In addition to this general revision.
however, we have extended the book in three main directions.
The book as originally planned was intended to meet the needs
primarily of pupils'in the senior forms at schools and of under-
graduates up to the level of a Pass Degree. We have extended
Parts II and III dealing with Preparations and with the Reactions
and Identification of Organic Compounds so that the book should
now cater fully for the needs of students working for Honours
Degrees. In particular, the Preparations now include examples
of most of the more simple standard reactions: for this pur-
pose we have now added, for example, preparations illustrating
the Benzidine Transformation, the Ullmann Condensation,
the Benzilic Acid Rearrangement, the Reformatsky Reaction, the
Clemmensen Reduction, the Fischer Indolisation Reaction, the
Mannich Reaction, and the Diels-Alder Reaction. It is probable
that preparative work on a much smaller scale than has hitherto
been customary in teaching laboratories will become more
common in future. To meet this need, we have added a short
section to Part I, describing the design and use of apparatus for
this purpose, and we have also included some examples of these
small-scale preparations as alternatives to the larger preparations
in Part II.
In Part III, dealing with the Reactions and Identification of
Organic Compounds, greater emphasis has now been placed on
the preparation of suitable crystalline derivatives. Quite apart
from the importance of these derivatives for purposes of identi-
fication, encouragement is thereby given to the student to gain
experience in small-scale preparative work.
We have also added an entirely new section dealing with semi-
microanalysis. In our original Introduction (p. ix) we justified
the retention of macro-methods of quantitative analysis on the
grounds that they formed an excellent introduction to micro-
methods and also afforded a valuable training in exact manipula-
tion generally. By now, however, the macro-estimation par-
ticularly of carbon and hydrogen and of nitrogen has disappeared
entirely from most laboratories. On the other hand, the micro-
PREFACE TO THIRD EDITION xi
methods developed so largely by Pregl, and which usually require
no more than 5 mgm. of material, necessitate prolonged training
and an impeccable experimental technique, and give consistently
reliable results only in the hands of full-time analysts. They are
consequently unsuitable for students. The semi-micro methods
of analysis, which usually require 20-50 mgm. of material, form
an ideal compromise for student-training, for the necessary
technique can be acquired after only a few attempts. These
methods moreover provide the student with very valuable
manipulative exercise, and serve as an introduction to the hand-
ling of even smaller quantities of material which may arise in
his post-graduate work. This section on Semi-microanalysis has
been designed and written by Dr. P. Sykes, and is based on his
experience of teaching such methods in the Cambridge labora-
tories. We wish to thank him sincerely for a valuable contribution
to this work.
In the original planning of this book we were at pains to
ensure that the preparations in particular were designed to
afford a minimum expenditure of time, materials and heating.
We hope that the economy thus introduced will be especially
appreciated in view of the recent heavily increased cost of
chemicals, fuel and laboratory service. This increased cost,
incidentally, must necessarily increase the attraction of the
small-scale preparations referred to above.
We are grateful to our colleagues for many valuable discussions
and suggestions: in particular we would mention Dr. F. B.
Kipping, Dr. P. Maitland, Dr. G. W. Kenner and Mr. J. Harley-
Mason.
We should also like to express once again our sincere thanks
for the considerable help we have received from our laboratory
assistants, Mr. F. C. Baker and Mr. F. E. Smith.
F.G.M.
B.C.S.
PREFACE TO SECOND EDITION

THE two chief additions which have now been made are the
Sodium Carbonate-Zinc Method as an alternative to Lassaigne's
Sodium Fusion Method for detecting elements in organic com-
pounds, and the Tables of Physical Constants which have been
included in the Appendix. These Tables have been compiled
to cover a very much wider scope of organic compounds than
those described in this book. In addition to the general utility
of these Tables, we hope that they will be of value to students
wishing to extend their practice in the identification of organic
compounds beyond the range given in Part III of this book.
This range has been deliberately limited in order to enable
students to obtain a firm grasp of the methods of identifying
simple compounds, and these methods have therefore been based
almost entirely on chemical reactions alone. When the range of
organic compounds to be identified is extended, and particularly
when higher homologues are being investigated, identification by
the physical properties of derivatives becomes increasingly
necessary, and the Tables of Physical Constants should con-
siderably facilitate this extension.
We wish to express our gratitude to the chemists who have
made suggestions with regard to the subject-matter of this book:
many of these suggestions have now been incorporated in this
edition. Wre would warmly welcome further suggestions for
improving its contents.
F.G.M.
B.C.S.
INTRODUCTION
THIS laboratory manual of organic chemistry has been compiled
primarily to cover the work required for Part I of the Natural
Sciences Tripos at Cambridge University, the General B.Sc.
course at London University, and the Pass Degree courses at
other universities. At the same time, however, it has been
carefully arranged to cover adequately the needs of students pro-
ceeding to the M.B. examinations in organic chemistry at the
various universities. Moreover, since the introductory work
has been given in considerable detail, the book is suitable for
senior pupils at schools (more particularly for Higher Certificate
and University Entrance Scholarship candidates), and should
therefore be sufficient to cover both their school and university
needs.
This work is based largely on the authors' experience with the
teaching of practical organic chemistry to very large classes of
students at Cambridge University. For such classes experimental
directions involving the utmost economy in chemicals and
apparatus, and also in the students' time, are obviously required.
Therefore the whole of the experimental work described in this
book has been repeatedly checked by the authors themselves (and
for the most part by their classes also) in order to obtain the
desired results with a minimum expenditure of materials and
time. In the section on Organic Preparations in particular, this
detailed investigation of each preparation has frequently enabled
unexpected simplifications and economies to be introduced, more
particularly as many text-books still contain experimental direc-
tions which have frequently remained unchanged since their
original publication in chemical journals many years ago, and
in which, moreover, occasional errors both in fact and in tran-
scription have thus remained uncorrected. It is almost uni-
versally found that departments of organic chemistry are more
costly to maintain than other science departments, primarily
because of the heavy consumption of organic reagents and sol-
vents, and the economies which have now been effected will, we
think, be appreciated by most teachers of practical organic
chemistry.
Teachers of chemistry (and of the sciences generally) will have
found that many students appear to dissociate their practical work
sharply in their minds from their theoretical knowledge. Many
xiii
xiv INTRODUCTION
students of organic chemistry moreover remain familiar with a
particular preparation, but fail to appreciate the value or
significance of the process of which that preparation is merely one
example: for instance, a student may often have a detailed
knowledge of the preparation of acetanilide, but be unable to
give a general account of the methods of acetylation, or of the
practical value of the process of acetylation itself. Consequently
in the following pages the description of most experiments (and
particularly of the preparations) is preceded by a short account in
small print of the chief theoretical considerations involved: in
the case of preparations based on one of several alternative
methods, a brief account is similarly given of these methods and
of their comparative practical value. This combination of theory
and practice will, it is hoped, both simplify and elucidate the
practical study of organic chemistry, and enable the student to
visualise his practical work as an orderly whole and not as a vast
number of isolated and unrelated experiments.
Part III, on the Reactions and Identification of Organic
Compounds, has been strictly limited to the commoner members
of each of the more important classes of organic compounds.
This work, consisting chiefly of reactions carried out on the test-
tube scale, should be of great value to the student, who, if he
carries out the reactions intelligently, should thereby effectively
consolidate his theoretical knowledge. Yet students frequently
attempt far too ambitious a programme of reactions and more
particularly of qualitative analysis, and thus often become lost in
the very detailed work on which such programmes are based. We
consider therefore that students should master thoroughly the
more simple programme given in Part III before proceeding
to wider and more detailed systems for the identification of
organic compounds.
The comparatively wide prevalence of micro-methods of quan-
titative organic analysis, applied more particularly to the estima-
tion of the constituent elements in an organic compound, may
cause the advisability of including the macro-methods in Part
IV to be questioned. Quite apart, however, from the fact that
the micro-methods still find no place in many laboratories, we
consider that thorough practice in the macro-methods of quanti-
tative analysis to be not only an excellent introduction to the
micro-methods themselves, but also a valuable training in exact
manipulation generally.
Part V, on Simple Enzyme Reactions, is rather a new de-
parture in practical books of this type. The importance of
INTRODUCTION xv
this section to medical students, biochemists, physiologists, etc.,
is obvious. We consider, however, that students of chemistry
who are not reading any biological subject should have some
practical knowledge of a branch of organic chemistry which is of
the greatest scientific importance, and the industrial application
of which will undoubtedly increase very widely in the future. At
present it rarely occurs to such students that an organic reaction
can be usefully promoted by the application of anything but the
flame of a Bunsen burner!
If students are carefully trained in accurate work, accidents in
the laboratory should be of very rare occurrence. Since, however,
they can never be entirely eliminated, it is hoped that the First
Aid directions given in the Appendix will prove of value, particu-
larly to the junior staff of laboratories, who by virtue of their
duties as demonstrators are frequently the first to be called upon
to help injured students.
We wish to express our very sincere thanks to Dr. W. H Mills,
F.R.S., and to Dr. Hamilton McCombie, for much advice and
help in the compilation of this book; to Prof. C. S. Gibson,
F.R.S., for suggestions with regard to the needs of medical
students; and to Prof. E. L. Hirst, F.R.S., for advice upon
certain preparations in the carbohydrate series. We are also
greatly indebted to Dr. F. B. Kipping and Dr. P. Maitland for
many suggestions based on the experience obtained from their
own first-year medical and Tripos classes. We gratefully acknow-
ledge the help we have received from Dr. P. J. G. Mann of the
Cambridge University Biochemical Department, who read over
the section on Enzymes and made many valuable suggestions, and
from Dr. F. J. W. Roughton, F.R.S., and Dr. G. A. Millikan, who
kindly furnished the details of experiments concerning carbonic
anhydrase.
Our warm thanks are due also to our Laboratory and Lecture
Assistants, Mr. F. C. Baker and Mr. F. E. Smith, who have given
us great help in the many repetitions of the preparations and the
quantitative analyses respectively which were required before
this book could attain its final form.
The notes on First Aid have been based on the memorandum
Safeguards in the Laboratory, compiled by the Science Masters.
Association and the Association of Women Science Teachers.
This report has, however, been considerably modified and
amplified for our purpose, and we are greatly indebted to t)r.
F. B. Parsons, M.D., for very kindly supervising our final draft
and thus ensuring its medical accuracy.
xvi INTRODUCTION
The authors will welcome criticisms and suggestions from
teachers of practical organic chemistry.
Cambridge. F. G. MANN
May 1936 B. C. SAUNDERS
CONTENTS
PAGE
Part I. METHODS AND MANIPULATION i
ADVANCED TECHNIQUES OF SEPARATION AND
PURIFICATION . 4 8
METHODS AND MANIPULATION ON A SEMI-MICRO
SCALE . . . . . . . . 5 9

Part II. PREPARATIONS 73


Part III. REACTIONS AND IDENTIFICATION OF ORGANIC
COMPOUNDS 316

Part IV. QUANTITATIVE ANALYSIS . . . . . 4 1 6


SECTION A
MACROANALYSIS . . . . . 4 1 6
SECTION B
SEMI-MICROANALYSIS . . . . . 4 6 5

Part V. SIMPLE ENZYME REACTIONS 509


APPENDIX
PREPARATION OF REAGENTS . . . . 5 2 4
FIRST-AID, TREATMENT OF FIRES, ETC. . . 5 2 6
TABLES I-XXVIII . . . . 533
INDEX . . . . 566

xvn
SAFETY PRECAUTIONS

to be observed during Laboratory Work.

(1) Protection of the eyes. Safety goggles should always be


worn over the eyes, especially when carrying out potentially
dangerous operations, e.g., vacuum distillations, distillation of
large volumes of inflammable liquids, and experiments requiring
large quantities of metallic sodium.

For treatment of injuries to the eye, see p. 527.

(2) Cuts. Most cuts which occur in the laboratory are caused
either by glass tubing, condensers, etc., snapping while being
forced through perforated corks, with the result that the broken
jagged end cuts the hands holding the cork, or by test-tubes,
boiling-tubes and heavier glass cylinders breaking whilst being
too forcibly corked, with similar results. Such accidents in either
case are avoided by careful working.
For treatment of cuts, see p. 528.

For First-Aid Directions, see p. 526.

xvm
ABBREVIATIONS
The following abbreviations are used throughout this book:
b.p. . . . . . boiling-point
f.p. . . . . . freezing-point
m.p. . . . . melting-point
d. . . . . density (g. per ml.)
g gram(s)
1 litre(s)
mg. . . . . . milligram(s)
ml. . . . . . millilitre(s)
G.MoI. . . . . gram-molecule
M Molar
N. . . . . . Normal
Atm. . . . . Atmosphere-pressure
S.T.P. . . . . Standard temperature
and Pressure
The density of liquids, unless otherwise stated, is given at i5°C.

The experiments described in Part I have been numbered, as


they form a graded series to illustrate the chief manipulative
processes employed in practical organic chemistry. The experi-
ments in Parts 11-V have not been numbered, as in general a
selection must be made from them. In each part of the book,
the experiments have been arranged as far as possible in logical
order, although occasionally (as in Part IV) this is not necessarily
the order of increasing difficulty.

XlX
PART I
METHODS AND MANIPULATION
IN this part of the book, a brief account is given of the chief
manipulative processes which are used in practical organic
chemistry. Most of these processes are those which students are
likely to use repeatedly in their work. The remainder are not of
such frequent occurrence, but are processes with which more
advanced students should be familiar: the discussion of the latter
processes is given in small print.
It should be emphasised that all the processes here described
are considered essentially from the practical standpoint. The
student should always acquaint himself with the theoretical basis
of these operations, for which he should consult any standard
text-book of physical chemistry: this applies particularly to such
processes as the distillation of constant boiling-point mixtures,
steam-distillation, ether extraction, etc.
The experimental operations in organic chemistry which occur
with greatest frequency are those which are concerned, directly
or indirectly, with the isolation and purification of organic
compounds. It is necessary therefore to describe in detail the
chief methods of purification. Before doing so, however, the
criteria of purity (and their observation) must first be discussed,
so that when the purification has been attempted, its success can
at once be checked and confirmed.
Criteria of Purity. Solid Compounds. The property of
an organic compound which is most frequently determined as a
criterion of purity is the melting-point, because in general it may
be said that a pure compound has usually a sharp melting-point
(i.e., the substance melts entirely within a range of about I 0 C.),
whereas an impure substance has an indefinite melting-point, and
will therefore melt slowly and indecisively over a range of several
degrees. The actual possibilities which may be revealed by a
melting-point determination may be summarised as follows:
A. Melting-point sharp.
(1) Substance chemically pure. This is almost invariably the
cause of a sharp melting-point.
(2) Substance is a eutectic mixture of two or more compounds.
The chance of a given mixture containing two compounds
2 PRACTICAL ORGANIC CHEMISTRY
in just the proportion to give a sharp-melting eutectic
mixture is so remote that this possibility may be neglected.
[Occasionally arbitrary mixtures of two substances which
(usually) are chemically related may melt fairly sharply at
temperatures intermediate between the melting-points of
the two components, but this phenomenon is rarely
encountered.]
B. Melting-point indefinite.
(1) The substance is impure. This is almost invariably the
cause of an indefinite melting-point.
(2) The substance is pure, but on warming undergoes slight
thermal decomposition before the melting-point is reached,
and the decomposition products then act as impurities and
depress the melting-point.
Experimental Determination of Melting-point. The
general method consists in placing the finely powdered compound
in a capillary tube, and heating the latter in a bath of a suitable
liquid, the temperature of the bath when the compound melts
being then noted. The capillary tubes should be very thin-
walled tubes, about 8 cm. long, and about i mm. in diameter.
They can be prepared very easily by heating the centre of a clean
dry soft-glass test-tube* in a large brush flame of a Bunsen
burner, whilst the ends of the tube are uniformly rotated by the
hands. When the central portion of the tube over a length of
about 5 cm. has become both soft and moderately thickened by
the heating, the ends of the tube are drawn as far apart as the arms
permit, the soft portion of the tube being thus drawn out into a
long capillary. The latter is then cut into suitable lengths
(rejecting any flawed or otherwise unsuitable portions), and one
end of each portion is then sealed. This is done by inserting the
end of the capillary tube horizontally into the extreme edge of a
small steady Bunsen flame for a few seconds, rotating the capillary
meanwhile: no difficulty should thus be experienced in obtaining
a uniformly sealed strong end to the capillary tube (Fig. I(A)).
A clean dry porous plate is then broken into fragmentsj* about
* A laboratory demonstration of this operation is far better than any written
description. The tubes may be bought from many dealers (e.g., A. Gallenkamp
& Co. Ltd., Technico House, Christopher Street, London, EC2P 2ER, and
Victoria House, Widnes, Lanes; also The Scientific Glass-Blowing Co., 41
Upper Brook Street, !Manchester 13), but students should learn to make their
own capillary tubes.
f A microscope slide may be used in place of the fragment of unglazed
porcelain. The slide has the advantage that it can be washed after each determin-
ation and so used repeatedly: the rough surface of the porcelain, however,
lends itself much more readily to the pulverisation of the organic material.
METHODS AND MANIPULATION 3
3 cm. square. (A supply of the fragments in a dust-tight box
should always be freely available in the laboratory.) To fill the
capillary with the compound the melting-point of which is to be
determined, about 0-05 g. of the compound is placed on one of the
fragments of plate, and crushed to a fine powder by gently rubbing
it with the flat end of a porcelain spatula or (better) with the
slightly bent end of a small flat narrow metal (e.g., nickel) spatula.
When a very fine powder has been obtained, sufficient is trans-
ferred to the capillary tube (by pushing the open end of the tube
through the powder and backing the latter if necessary with the
spatula) so that, when the closed end of the tube is tapped on the
bench, a length of about 5 mm. of fairly tightly packed material
has accumulated at the bottom. This is a rapid operation when
the compound gives a fine dense powder: some compounds how-
ever, even when pure, have a waxy consistency, and are not easily
inserted into a tube of the usual width, in which case a slightly
wider capillary (say 2 mm. in diameter) may have to be used. The
student should soon be able by experience to select a suitable
tube having once obtained the "feel" of the material when
crushed on the porcelain. Should the material be inclined to
stick in the tube, it can often be rapidly conducted to the bottom
by vibrating the tube gently by the cross-wise action of a blunt
file or the milled edge of a coin.
The usual apparatus for
heating the substance is
shown in Fig. I(B), and RB

consists of a long-necked
hard-glass flask D to which |J
a thermometer E is fitted
by means of a cork having
a shallow vertical groove F
cut or filed as shown to
allow expansion of the RB
contents of D. The best
liquid for placing in D is
medicinal paraffin, which
possesses the following
very suitable properties:
(a) it has a low specific
heat and therefore the tem-
perature can be easily
increased using only a small (B)
flame, (b) even when hot it FIG. i.
4 PRACTICAL ORGANIC CHEMISTRY
is almost non-inflammable, and therefore should the flask break
whilst still over the flame, the oil seldom ignites, (c) the oil is
non-corrosive, and owing to its low specific heat causes remark-
ably slight burns even if spilt, while at a high temperature, on
the hands. The oil may be safely heated up to about 220°, when
it begins to decompose slightly, giving off smoky fumes. For
substances melting above this temperature, the flask D should
contain concentrated sulphuric acid containing a crystal of
potassium nitrate to prevent charring and consequent darkening
in colour at higher temperatures. Fresh sulphuric acid can
be safely heated to about 280°, but its use should generally be
avoided in elementary classes. Alternatively, silicone* can be
used in place of sulphuric acid for compounds of high melting-
point. It is a straw-coloured non-corrosive liquid which can be
safely heated to ca. 300° without decomposition or ignition.
The capillary tube is then placed as shown against the ther-
mometer E, to which it will adhere by the capillary attraction of
the oil, the column of powdered material being thus beside the
bulb of the thermometer. The oil in D is then slowly heated,
and the temperature, or range of temperature, over which the
compound melts carefully noted. It is essential for an accurate
determination that the temperature of the oil in D should rise
very slowly as the compound is about to melt. It will therefore
frequently save time, particularly if the compound is likely to have
a high melting-point, to fill two capillaries with the substance.
The temperature of D ife then raised quickly using one tube, in
order to determine the melting-point approximately: the tem-
perature is then allowed to fall about 30°, the second capillary
is then substituted for the first, and an accurate determination
with the temperature very slowly rising is then made. It is
important to note that a second determination is never made by
noting the temperature at which the molten material in the
capillary solidifies as the oil cools, or by reheating the tube after
this solidification has occurred.+ A freshly-filled capillary should
always be used for each subsequent determination.
The more accurate apparatus shown in Fig. i(c) is strongly recom-
mended when laboratory conditions enable students to retain their own
apparatus over a complete course of work. A glass tube T, bent as
shown, is fixed by the rubber-bands RB to the thermometer G. The
* Marketed as "DC55O Fluid" by Midland Silicones Ltd., Oldbury, Bir-
mingham, and obtainable from Hopkins & Williams, Ltd, P.O. Box i, Romford,
RNl IHA.
f For an exception to this statement, sec Rast's Method, pp. 437, 438.
METHODS AND MANIPULATION 5
glass stirrer S is then placed so that the shaft is in the tube T, and is
connected by a piece of string through the tube as shown, a knot or a
cork preventing the stirrer from falling completely to the bottom of the
beaker H which contains the oil. The apparatus is kept permanently
fixed to a small retort stand, which holds the beaker on a gauze-
covered ring I, and the thermometer and tube by the clamp J. The
capillary is then placed as before against the thermometer, and the oil
gently heated: meanwhile by means of the string the stirrer is kept
steadily in motion and the oil well mixed. The thorough mixing of
the oil in this apparatus, and the better control of its temperature, give
therefore more accurate results than those obtained with the simple
apparatus shown in Fig. I(B).
The electrically heated type of melting-point apparatus, which
has certain advantages over the above types, is described on p. 6^,
Fig^ 33.

Experiment i. Determination of Melting-points.


The student should determine the melting-point of the follow-
ing compounds:
A (I). Pure Compounds, (a) Phenyl Benzoate M.p. 70°
(b) Benzoic Acid 121°
(c) Salicylic Acid 157°
By working in the above order, time will not be wasted by
having to allow the apparatus to cool between consecutive
determinations.
B (I). Impure Substances. Prepare an intimate mixture of (b)
with about one-third of its weight of (c).
(II). Pure Compounds, decomposing slightly before melting.
Lactose. Melts slowly between about 205 and 215°, with
preliminary darkening and subsequent decomposition.
NOTE. When it is suspected that an indefinite melting-point is
caused by a pure substance undergoing preliminary decomposition, a
fairly accurate result may often be obtained by repeating the determina-
tion, having first heated the oil to within 5-10° of the melting-point
before placing the capillary in position. The compound is thus
exposed to the high temperature for such a short time before melting
that only slight preliminary decomposition occurs.
Identification by Mixed Melting-points. It will be clear
that melting-point determinations afford a ready method of
identifying minute quantities of a solid compound, if the probable
identity of this compound is already suspected. Thus if there is
reason to believe that a particular substance is, for example,
6 PRACTICAL ORGANIC CHEMISTRY
benzoic acid, a small quantity of the substance is mixed with a
known sample of benzoic acid, and the melting-point of the
mixture determined. If the mixture has the normal sharp
melting-point of benzoic acid, then the unknown substance must
be benzoic acid itself: if the mixture has an indefinite melting-
point, then the unknown substance is not identical with benzoic
acid and by acting as an impurity is causing the indefinite melting-
point. Identification by "mixed melting-points" is a valuable
and frequently used process in organic research work.

Experiment 2. Identification by Mixed Melting-points.


Students should be provided with known (labelled) samples
of one of the following series of compounds, the samples being
finely ground so that no obvious difference in crystal form, etc., is
apparent. They should determine the melting-point of each
compound in order to assure themselves that these melting-points
lie too near together to enable any one compound to be identified
by a simple melting-point determination. They should then be
given an unknown compound A (preferably in coarse crystals),
told that it is one member of the series, and then identify it by
mixed melting-point determinations.
SERIES i SERIES n
Acetanilide M.p. 113° Benzoic acid M.p. 121°
Acetyl-o-toluidine 112° Succinic anhydride 120°
w-Toluic acid m° Hexacetylmannitol* 120°

SERIES in
Benzamide M.p. 130°
Phthalic anhydride 130°
p-Pentacetylglucosef 130°
Urea 132°
Corrected Melting-points. In all the above determinations of
melting-points, the values obtained are described as "uncor-
rected," since no allowance has been made for the fact that the
column of mercury in the thermometer is at a lower temperature
than that in the bulb. For most purposes it is sufficient to record
this uncorrected value, which is usually only slightly lower than
the corrected value.

Criteria of Purity. Liquid Compounds.


A pure liquid (which distils without decomposition) will have
* Preparation, p. 142. t Preparation, p. 141.
METHODS AND MANIPULATION 7
similarly a sharp boiling-point which will remain constant until
the whole of the liquid has boiled off, leaving no residue. Unlike
the melting-point, however, this boiling-point, whilst remaining
sharp, may vary in value over a range of several degrees, owing to
fluctuations in the barometric pressure. The boiling-point of an
impure liquid will depend largely on the physical nature of the
impurities. If all the impurities are non-volatile, the liquid will
have a sharp boiling-point, and the solid impurities will remain
behind when the liquid has evaporated. If the impurities are
themselves volatile, then the boiling-point of the liquid may (a)
remain constant (see below), or (b) rise steadily as the liquid boils,
or (c) rise in a series of definite steps, according to the nature and
quantity of the impurities present.
Although a pure liquid has a sharp boiling-point, the converse
is not necessarily true: a sharp boiling-point does not always
indicate a pure liquid, but may be caused by a constant-boiling
mixture of two or more liquids. Such mixtures are common in
both inorganic and organic chemistry: thus a mixture of 20-2%
HCl and 79-8% of water boils steadily at no°/76o mm.; a
mixture of 60-5% benzene and 39-5% methanol has boiling-
point 58'3°/76o mm.; a mixture of 14% of ethanol and 76%
ethyl iodide has boiling-point 63-07760 mm. The difference
between a pure liquid and a constant-boiling mixture can
easily be detected by redistilling at a different pressure. A
pure liquid under these conditions will change its boiling-point,
but the composition of the distillate will necessarily remain un-
changed: a constant-boiling mixture will however change both
in boiling-point and in the composition of the distillate. This
change in composition can then be detected by analysis, density
determinations, etc.
As a guide to the probable occurrence of a constant-boiling mixture,
it should be noted that such mixtures most frequently occur when one
of the components contains an hydroxyl ( — OH) group. Only aqueous
and alcoholic mixtures therefore are likely to have a constant boiling-
point.

Experimental Determination of Boiling-point. Unless


only minute quantities of the liquid are available (c/. p. 60), the
boiling-point is usually determined by simple distillation. For this
purpose, the apparatus shown in Fig. 2 is assembled. A distilla-
tion flask A of suitable size is fitted to a water-condenser B, the
water supply of which is arranged as shown. An adaptor C is
sometimes fitted in turn to the condenser, so that the distillate
8 PRACTICAL ORGANIC CHEMISTRY
may be collected directly into a suitable flask D, but the use of an
adaptor in this way is seldom necessary. The liquid is then
placed in the flask A (which should not be more than three-
fifths filled), some small fragments of unglazed porcelain*
added, the thermometer E placed in position, and
the flask then heated—either on a water-bath if the
liquid has a low boiling-point, or else on a sand-bath,
or directly over a wire gauze. The following important
points with regard to simple distillation should be
noted:—
(i) The fragments of
unglazed porcelain*
should always be added
whenever a liquid is
boiled, in order to
provide nuclei for the
formation of bubbles
of the vapour, and thus
ensure steady, gentle
FIG. 2. boiling. If the por-
celain is omitted, the
liquid may become superheated, and then suddenly boil with
great violence. Fires are often caused by students omitting this
precaution when distilling inflammable solvents, which then
"bump" so violently that the liquid either pushes the thermo-
meter out of position and boils over, or else shatters the dis-
tilling-flask. Throughout this book, therefore, it is assumed that
porcelain is added whenever a distillation is described, and the use
of porcelain is mentioned only when it is particularly necessary.
(2) The thermometer should be so arranged that the top of the
bulb is just level with the centre of the side-arm of the distilling-
flask.
(3) A water-condenser can be used for any liquid the boiling-
point of which does not exceed 140°. Above this temperature, an
air-condenser (i.e., a straight glass tube having no jacket) should
be used. If a water-condenser is used above 140°, there is always
a risk of the condenser cracking at the point where the hot
vapour first meets the water-cooled portion.
(4) Low-boiling, inflammable liquids are usually distilled from
* Fragments ot unglazed porcelain can he replaced by small dark granules of
c a r b o r u n d u m (silicon carbide); these ensure steady boiling and remain active
\vhc-n the cold solution is reheated. Their accidental presence in subsequent
operations is immediately obvious.
METHODS AND MANIPULATION 9
a water-bath for additional safety. Whether a liquid can thus be
distilled from a boiling water-bath will depend chiefly on its
boiling-point and also on its latent heat, but as a general rule most
liquids of boiling-point below 80° may be distilled readily in this
way: for liquids of higher boiling-point a sand-bath or direct
heating on a gauze is necessary. Thus ethanol (boiling-point
78°) can be distilled from a water-bath: benzene (boiling-point
81°) will boil gently when heated on a water-bath, but not
sufficiently vigorously to distil over at an
appreciable rate. __
The water-condenser B shown in Fig. 2
represents the simplest and cheapest kind,
which because of its limited efficiency
should be at least 2 feet long. Fig. 3(A)
shows a bulb condenser, which, although
also cheap, is much more efficient. In Fig.
3(B) is shown the usual double-surface
condenser, which, although more costly
than the two former condensers, is far more
efficient, and need be only one-third to
one-half as long as the others. It should
therefore be available for reasonably care-
ful students.*
Modifications of the simple distillation are
described on pp. 23-24 under Purification of
Liquid Substances. FIG. 3.

Experiment 3. Determination of Boiling-point.


Most students will be familiar with simple distillation from
their practical inorganic chemistry. Other students should
determine the boiling-point of acetone (56°), using a water-bath
and water-condenser, or of benzene (81°), using a sand-bath and
water-condenser, and finally of either aniline (184°) or nitro-
benzene (210°), using for both these liquids a sand-bath and air-
condenser.
Filtration. Before discussing the practical details of the puri-
fication of solid substances by recrystallisation, it is convenient to
describe here the general methods of filtration. The two principal
occasions in organic chemistry when filtration is necessary are:
* A simpler \\ater-condenser having both ends comically ground (cf. (B),
p. 45), and a thin-walled inner tube, is lighter and more efficient than those
illustrated above.
io PRACTICAL ORGANIC CHEMISTRY
(A) A solid substance has crystallised from a solution, and it is
necessary to separate the crystals (i.e., the solute) from the cold
mother-liquor by filtration.
(B) A hot solution has to be filtered to remove traces of insoluble
impurities, and kept hot meanwhile to prevent crystallisation of
the main solute, which would otherwise choke up the filter.
(A) Filtration of crystals from the cold mother-liquor.
This type of filtration is almost invariably performed with the
aid of a Buchner flask and funnel, by means of which a rapid and
almost complete separation can be obtained. The Buchner flask
A (Fig. 4) consists of a simple thick-walled conical flask with a
short side-arm for connection to a water-pump. Into the neck of
the flask is fitted the Buchner funnel B which consists usually of
a cylindrical porcelain funnel, the bed of which is pierced by a
number of small holgs giving direct access
through the stem of the funnel to the flask.
Before filtration, one* layer of well-fitting
filter-paper is placed in the funnel B, and
moistened with a few drops of the liquid
to be filtered, so that when the suction
of the pump is applied the filter-paper
adheres firmly to the perforated bed of the
funnel, and thus subsequently prevents any
P solid matter from passing round and under
' *' the edge of the paper into the flask and so
avoiding filtration. The mixture of crystals
and solution is then filtered through the funnel under gentle
suction of the pump: when all the mother-liquor has been
filtered, some is returned to the vessel which originally contained
the mixture, and well stirred to remove any crystals adhering to
the sides of the vessel. This portion is then again filtered, and the
process is repeated until all the solid material has been trans-
ferred to the funnel B, and the whole of the mother-liquor has
collected in the flask A. The action of the pump is then con-
tinued until the crystals in B are thoroughly drained from traces
of the mother-liquor. If a large quantity of material is being
collected in the funnel, it should be pressed firmly down, e.g.
by a clean cork or stopper, during the draining. Students should
remember that the speed of filtration is not necessarily propor-
tional to the suction force of the pump. A gentle suction will
* Two layers of filter-paper are desirable for aqueous solutions: for organic
solvents, however, one layer is usually sufficient.
METHODS AND MANIPULATION ii
often cause rapid filtration, whereas increased suction may drag
the finer particles of the solute into the pores of the filter-paper,
and thus cause filtration to become very slow.
When only a small quantity of solid material has to be filtered
from a liquid, the small conical funnel C, usually known as a
Hirsch funnel, is used in order to collect and drain the material
on a very small filter-paper (see p. 68).
One disadvantage of porcelain Buchner funnels (particularly
when used in large classes) is the difficulty in detecting and
removing solid material which, owing to evaporation of the
filtrate, may have collected immediately below the perforated
plate. This difficulty is removed in the newer types of funnel
which are made of glass, and which have either a transparent
glass plate perforated by holes or fine slots, or a plate of fine
porous sintered glass. Although the glass funnels are more
fragile than the porcelain ones, they will undoubtedly replace the
porcelain funnels as they become cheaper.
More advanced students, who may frequently have occasion to filter
a very small quantity of crystals from a correspondingly small volume of
solution, are strongly recommended to use the Irvine filter-cylinder
(Fig. 5), which is invaluable for the clean, rapid and complete separation
of small crops of crystals. It consists of a glass
cylinder A, having at the base a simple tap B, and
at the side a two-way tap C, by means of which the
cylinder can either be connected directly through to
the pump, or alternatively connected through the
bottom of C to the open air, the pump being simul-
taneously cut off. A series of Buchner funnels, of Pump
various sizes and shapes, fit the top of the cylinder
as shown. A mixture of crystals and mother-liquor
in a beaker can therefore be filtered as usual through
the funnel D under suction of the pump. Rotation
of the tap C then cuts off the suction and relieves
the partial vacuum within the cylinder. The mother-
liquor can then be run through the tap B back into
the beaker, the tap B closed and C opened, thus
restarting the suction, and the beaker can then be
rinsed out with the mother-liquor, which is filtered FIG. 5.
again into the cylinder. The process is repeated
until all crystalline material has been transferred to D, where it is gently
pressed down with the spatula and thoroughly drained. If necessary,
the filtrate can be run out of A, and the crystals then washed with some
other liquid while still under suction on the filter.
(B) Filtration of hot solutions. The quickest method of
removing traces of insoluble impurities from a hot solution is to
12 PRACTICAL ORGANIC CHEMISTRY
filter it in the usual way through a Buchner funnel. The dis-
advantage of this method is that the heavy porcelain funnel may
so chill the solution that crystallisation occurs before filtration is
complete and the funnel may become choked with crystals, both
above the filter and below in the stem. The disadvantage may be
often overcome by boiling a quantity of the pure solvent (particu-
larly if the latter is water) and, immediately before filtration of the
solution, placing the filter-papers in the funnel and filtering a
moderate quantity of the pure boiling solvent through the funnel
into the flask. The solvent is then poured out, and the hot
solution at once filtered through the hot apparatus. This pre-
heating of both funnel and flask will often enable a hot solution
to be filtered and the clear filtrate transferred into a beaker before
any separation of solid matter occurs.
A "hot-water funnel" is a slower and less efficient apparatus
for filtering hot solutions. A satisfactory form of the apparatus
is shown in Fig. 6, in which the double-walled funnel is heated
by blowing steam through the apparatus as
Steam shown. A glass filter funnel of the usual type
fits snugly into the hot-water funnel. This
type has the advantage that, during the fil-
tration of a hot inflammable liquid, the steam
generator (and therefore the heating appar-
FIG. 6. atus) can be removed to a safe distance. It
should be noted that the inner glass funnel
should have a stem so short that it projects only just below
the outer metal funnel. If the stem is longer it serves merely to
cool the filtered solution, which may then crystallise and com-
pletely stop the filtration.
For the filtration of small quantities of dilute solution, it is
often possible to dispense with the outer heater, and use the
ordinary glass funnel which has been heated above a flame
immediately before use.
METHODS AND MANIPULATION 13
The filtration of any solution through the ordinary conical
funnel may be hastened considerably by the use of a "fluted"
filter-paper, instead of one folded into quarters in the usual way.
The folding of a fluted paper may be learnt far more readily by
a demonstration in the laboratory than by any written description.
The following is one of the simplest ways of fluting a filter-paper.
First make four folds in the paper so that the latter is divided into eight
equal sectors (Fig. 7(A)), the two halves of the paper on each occasion
being folded forwards, so that all the folds tend to be concave. Now
take each segment in turn (e.g., aOb, Fig. 7(8)) and fold the points a
and b backwards until they meet, so that a new convex fold Ox is made
between them: continue in this way making new folds Oy, Oz, etc.,
around the paper. When the complete fluted paper (Fig. 7(0)) is
placed in the ordinary conical funnel, it will possess a series of regular
corrugations, and only the edges of the folds Oa, Ob, Oc, etc., will be
in contact with the funnel.
Purification of Solid Substances.
Recrystallisation. The process of purification by recrystal-
lisation is undoubtedly the most frequent operation in practical
organic chemistry, and it is one which, when cleanly and efficiently
performed, should give great pleasure to the chemist, particularly
if the original crude material is in a very impure and filthy con-
dition. Yet no operation is carried out so badly, wastefully (and
thoughtlessly) by students in general, not only by elementary
students, but often by research students of several years' experi-
ence. The student who intends later to do advanced work must
master the process, for unless he can choose a suitable solvent and
then successfully recrystallise often minute quantities of material,
he will frequently find his work completely arrested.
Students are familiar with the general process of recrystallisa-
tion from their more elementary inorganic work. Briefly, it
consists in first finding a solvent which will dissolve the crude
material readily when hot, but only to a small extent when cold.
The crude substance is then dissolved in a minimum of the
boiling solvent, the solution filtered if necessary to remove any
insoluble impurities, and then cooled, when the solute will
crystallise out, leaving the greater part of the impurities in solu-
tion. The crop of crystals is then filtered off, and the process
repeated until the crystals are pure, and all impurities remain in
the mother-liquor.
Students are sometimes puzzled at the extraordinarily general appli-
cation of the process of recrystallisation, since it may appear to them to
depend on the assumption that the impurities are more soluble than the
14 PRACTICAL ORGANIC CHEMISTRY
main product, and therefore will always eventually be left in the mother-
liquor. Consideration will show that this assumption is not necessarily
made: the assumption actually made is that the impurities are either
more soluble than the main product, or, if less soluble, are present in
such small proportion that in spite of the comparative solubilities they
will be eliminated by recrystallisation. The two cases may be exempli-
fied thus. Suppose the crude mixture contains 97% of the required
compound A, and 3% of an impurity B. Then if
(1) A is less soluble in a given solvent than B.
It is clear that repeated recrystallisation will rapidly leave B entirely
in the mother-liquors, and thus provide a pure sample of A.
(2) A is more soluble in the solvent than B.
Suppose that a given volume of the solvent when cold can dissolve
15 g. of A and 5 g. of B. If ioo g. of the crude product are dis-
solved in this volume of the hot solvent, and the solution allowed to
cool, then (ignoring the small mutual effect on the solubility of each
compound caused by the presence of the other) it is clear that 82 g.
of A will crystallise, whilst the whole of B will remain in solution, since
the latter is not saturated with respect to B.

The choice of a solvent is of course determined primarily by


its suitability for the actual recrystallisation of the given crude
product. If two or more solvents appear to be almost equally
suitable for the recrystallisation, the final choice should depend
on the inflammability (and therefore risk in use) of the solvent,
and also on its cost. It is assumed that a solvent which might
have any chemical action on the compound has already been
debarred. The chief solvents normally available are:

Solvent. B.P. Inflammability. Remarks.


Water 100° Non-inflammable To be used whenever
(distilled) suitable.
Ether 35° Inflammable Avoid when possible
(see below).
Acetone 56° ,, Should preferably be
dried before use.
Methanol 65° „ Toxic
Benzene 81° ,, ,,
Petroleum Available in ,, Frequently called
fractions of "light petroleum" or
b.p. 40-60°, "petrol ether." Un-
60—80°, less specially purified,
80-100°, contains sulphur de-
100-120° rivatives, etc., as
impurities.
METHODS AND MANIPULATION 15
Solvent. B. P. Inflammability. Remarks.
Acetic acid 118° Not readily Hygroscopic. Hot
(glacial) inflammable liquid gives pungent
fumes. Frequently
Ethanol used to dissolve
(a) Absolute ethanol. Anhydrous, but contains some Strong OXldlSing
benzene from azeotropic distillation of (b) with agents fo 2CO^
benzene. agciiu* ^p. £$y)'
(b) Rectified ethanol, contains 95-6% ethanol, 4'4°o
water. Care in using it with hygroscopic sub-
stances.
(f) Colourless industrial methylated spirit [I.M.S.],
contains 95 vols of (6) and 5 vols of wood
naphtha.

Chloroform 61° Non-inflammable May contain traces of


HCl, due to oxida-
tion or hydrolysis.
Carbon 77° „
tetrachloride
Carbon disulphide should never be used if any alternative
solvent is available, as it has a dangerously low flash-point, and
its vapours form exceedingly explosive mixtures with air. Ether
as a solvent for recrystallisation is much safer than carbon di-
sulphide, but again should be avoided whenever possible, partly
on account of the danger of fires, and partly because the filtered
solution tends to creep up the walls of the containing vessel and
there deposit solid matter by complete evaporation instead of
preferential crystallisation.
Homologous mono-alkyl ethers of ethylene glycol, such as mono-
ethyl glycol (or 2-ethoxyethanol), HOC 2 H 4 OC 2 H 5 , form excellent sol-
vents as they combine to a large extent the solvent properties of alcohols
and ethers. The monoethyl and the monomethyl members have the tech-
nical names of ethyl cellosolve and methyl cellosolve respectively. Dioxan
pTT pT_T
(or diethylene dioxide) O<^pTT 2 pir 2 /O, and dimethylformamide,
HCON(CH3)2, also possess exceptional solvent properties. The alkyl-
glycols, dioxan and dimethyl-formamide should be used with caution,
however, as their hot vapours are poisonous.

Experimental Directions for Recrystallisation. The


complete process consists of the following stages, each of which is
discussed in full:
(i) Choice of a Solvent. No theoretical considerations are of
any real use for this purpose, except the very rough generalisation
that a solvent will dissolve most readily compounds similar in
16 PRACTICAL ORGANIC CHEMISTRY
constitution to itself: thus alcohol will usually dissolve other
hydroxy compounds, benzene will dissolve hydrocarbons, etc.,
but there are many exceptions to this rule. Therefore the
experimental determination is alone of value.
Place about o-i g. of the crude powdered compound in a
clean dry test-tube, and add sufficient of the possible solvent just
to cover the compound. If the compound dissolves readily in
the cold, the solvent is obviously unsuitable. If it does not
dissolve, warm the mixture gently over a very small Bunsen
flame until the liquid boils: it is advantageous at this stage to
hold the forefinger loosely over the mouth of the tube to prevent
undue loss of vapour. Continue adding the liquid if necessary
until almost all the substance has dissolved. If a large amount of
the solvent is required (e.g., one-half to two-thirds of the tube)
then the low solubility renders the solvent unsuitable. If an
almost clear solution is obtained, cool by immersing the tube
preferably in a mixture of ice and water, or alternatively in cold
water. (If benzene is the solvent, cold water alone must be used,
as benzene will itself crystallise in ice-water.) Shake the mixture
gently in the tube. If crystallisation does not rapidly start, the
failure may be due to lack of suitable nuclei for crystal-growth.
Therefore scratch the tube below the surface of the solution with
a glass rod: the fine scratches on the walls form excellent sites for
crystal-growth, and crystals often form rapidly after scratching.
Repeat this process with various other possible solvents (using a
fresh clean tube for each test) until the best solvent has been
selected, and then note carefully the approximate proportions of
the solute and the solvent for efficient recrystallisation.
Sometimes the crude substance may contain an insoluble impurity,
and on cooling the solution it may be difficult to judge how much of the
solid matter is merely undissolved impurity and how much is solute
which has subsequently crystallised from solution. To avoid this
difficulty, the hot solution should be filtered, and should thus always
be absolutely clear before cooling is attempted. Therefore filter the
hot solution into a clean tube through a very small fluted filter-paper
contained in a correspondingly small glass funnel, which should have had
its stem cut off as that shown in Fig. 6, p. 12 (and for the same reason).
Unless the upper part of the filter is cut away to reduce its size to a
minimum, a large proportion of the solution will remain held mechani-
cally in the pores of the paper itself and only a few drops of clear filtrate
will be obtained.
(2) Repetition of Recrystallisation on Larger Scale. Having
now determined both the best solvent and also the approximate
METHODS AND MANIPULATION 17
proportions of solute and solvent for recrystallisation, the main
bulk of the crude material may be recrystallised. If the solvent
is water, the material is placed in a beaker or (better) in a conical
flask, and a volume of water which is judged to be just insufficient
for the purpose is then added, and the mixture gently heated
(with the usual addition of fragments of unglazed porcelain) to
boiling. More water is then cautiously added until either a clear
solution is obtained or until the undissolved material is recognised
from the experience gained in (i) as being insoluble impurity.
In either case, the boiling solution is then filtered. For this
purpose steps must be taken to prevent undue cooling of the
solution during filtration, otherwise crystallisation will occur
prematurely and choke the filter. This applies more particularly
of course if the preliminary test in (i) has shown that crystallisa-
tion starts very rapidly on cooling the hot solution. Therefore if
a Buchner funnel and flask are used, this apparatus must usually
be preheated by the filtration of some pure boiling water, as
described on p. 12, or alternatively a heated funnel must be
used.
If an organic solvent is used, boiling in an open vessel is
obviously not permissible, as the operation would be wasteful in
all cases, and dangerous with an inflammable solvent.
The crude material is therefore placed either in a
round-bottomed bolt-head flask (Fig. 8) or in a
conical flask, the solvent added (again in slight
deficiency) and a reflux water-condenser fitted to
the flask as shown. The mixture is boiled either on
a water-bath or over a gauze, and then more solvent
added cautiously down the condenser until a clear
solution (apart from insoluble impurities) is again
obtained. It is then filtered hot as described above.
The hot filtered solution is then without delay
poured into a lipped beaker or a conical flask (not
into an evaporating-basin, since it is crystallisation
and not evaporation which is now required), the
beaker covered with a watch-glass, and then cooled
in ice-water. As cooling proceeds, the solution should
IG
be stirred from time to time to facilitate crystallisa- * '
tion, and when crystallisation appears complete, the cooling
should be continued for at least another 15 minutes.
Occasionally the solute may separate (particularly if strong external
cooling is rapidly applied) as a metastable oil or syrup, which solidifies
on standing although a considerable interval may elapse before crystal-
18 PRACTICAL ORGANIC CHEMISTRY
lisation occurs. This should be avoided, for even if the oil subsequently
crystallises well, it will probably occlude a moderate quantity of crude
mother-liquor, and its purity will therefore not be high. In such cases
it is best to re-heat the mixture until a clear hot solution is obtained,
and then allow it to cool spontaneously, stirring and scratching with a
glass rod from time to time. It is thus often possible to induce crystal-
lisation to start, and it will then proceed without the production of the
less stable oil. During the cooling and scratching, a minute quantity of
the crude material may occasionally be added to " seed " the solution
and thus facilitate initial crystallisation. Formation of an oil or a syrup
on attempted recrystallisation is most likely to occur when an entirely
new preparation is carried out in the laboratory. When successful
recrystallisation is once accomplished, the laboratory becomes " inocu-
lated " with nuclei of the crystals, and subsequent recrystallisation
usually proceeds readily.* Hence this difficulty is far more likely to
occur in a research laboratory than in one in which routine preparations
are repeated at regular intervals.
\Vhen an organic substance is found to be freely soluble in one solvent
and insoluble in another, a mixture of these solvents (if miscible) will
often prove excellent for recrystallisation, the best proportion of the
two solvents in the mixture being found by small-scale tests. It some-
times happens, however, that the solute (particularly if it possesses a
rather low melting-point) separates from such a mixture as a fine
emulsion, which solidifies on further cooling. In such cases, a hot
concentrated solution of the crude substance should be prepared in the
liquid (e.g., ethanol) in which it is freely soluble, and then the other
liquid in which it is almost insoluble (e.g., water) should be added drop
by drop with stirring until an emulsion or a cloudiness just appears. A
clear solution is now again obtained either by warming momentarily,
or by adding SL few drops of the first solvent, and it is then allowed to cool
spontaneously: if the cloudiness should reappear, a few more drops of
the first solvent are added. A clear solution can thus be maintained
until the temperature has fallen so low that crystallisation starts: the
solution can then be stirred and cooled without further risk of emulsion-
formation. Examples of this process are described for o-nitrophenol
(p. 172) and amino-azobenzene (p. 209).
When crystallisation is complete, the mixture of crystals and
crude mother-liquor is filtered at the pump, again using a Buchner
funnel and flask as described on p. 10, and the crystals remaining
in the funnel are then pressed well down with a spatula whilst
continual suction of the pump is applied, in order to drain the
mother-liquor from the crystals as effectively as possible. If it
has been found in the preliminary tests that the crystalline
material is almost insoluble in the cold solvent, the crystals in the
* For an example, see p. 143.
METHODS AND MANIPULATION 19
funnel, after a short preliminary draining from the mother-liquor,
may be quickly washed on the filter with a small quantity of the
pure solvent, and the draining continued without interruption.
An efficient removal of traces of the mother-liquor can thus be
effected.
(3) Drying of Recrystallised Material. It is now required to
obtain the recrystallised material in a thoroughly dry condition
and this can seldom be achieved solely by draining on the filter.
One rapid method of drying the thoroughly drained material is
to transfer it with the aid of a spatula on to a pad of several thick-
nesses of drying paper (i.e., coarse-grained, smooth-surfaced
filter-paper), place a similar pad on top and then press the material
strongly, occasionally transferring it to fresh paper as the earlier
sheets become too soiled by the mother-liquor absorbed. The
final traces of mother-liquor can then be rapidly removed (if the
material is physically and chemically stable up to 100°) by drying
in a steam or electric oven. The chief disadvantage of this
method however is that the recrystallised material is always apt to
become contaminated with filter-paper fibre, and moreover a
well-crystallised material may
be crushed by the pressure to
a fine powder. If time per-
mits, therefore, the drained
material should always be
finally dried in a desiccator.
For this purpose the simple
and inexpensive atmospheric
desiccator (Fig. Q(A)) is fre-
quently used: the drying (A)
agent employed is usually
calcium chloride, or small
uniform fragments of silica gel. The latter are coloured blue with
a cobalt salt, and their colour changes to red as the material
becomes spent: it can be regenerated by heating. Far more rapid
and efficient drying is, however, obtained with a vacuum desic-
cator of the type shown in Fig. 9(8).
A very effective "universal" filling for vacuum desiccators is obtained
by having concentrated sulphuric acid C in the bottom of the desiccator,
and "flake" sodium hydroxide* D in the inverted glass collar supported
on the shoulders of the desiccator, the collar then being covered
• Supplied as "flake" or "petal" sodium hydroxide by chemical manufac-
turers.
20 PRACTICAL ORGANIC CHEMISTRY
with wire gauze. Very rapid drying is thereby obtained, and any
acid or basic vapours which may be evolved are absorbed, the interior of
the desiccator thus remaining clean and odourless. This is of particular
advantage when drying a substance, e.g., an amine hydrochloride,
which has been recrystallised from concentrated hydrochloric acid,
and which would otherwise fill the desiccator with hydrogen chloride as
drying proceeded.
If a compound has been recrystallised from petrol, benzene, etc.,
some freshly cut shavings of clean paraffin wax should be added to the
calcium chloride in (A) or to the sodium hydroxide in D. The surface of
the wax absorbs organic solvent vapours (particularly the hydrocarbons)
and the last trace of such solvents is thus readily removed from the
recrystallised material.
When using a desiccator, the recrystallised material in the
Buchner funnel should be transferred to a piece of clean glazed
paper with the aid of a spatula, and the last traces carefully
removed from the sides of the funnel and the damp filter by
careful use of the spatula, in such a way that the surface of the
filter is not torn or scratched, and that filter-paper fibre does not
contaminate the crystals. The latter can then be tipped without
loss from the glazed paper on to a watch-glass. If the atmospheric
desiccator (A) is used, the open watch-glass should be left in the
desiccator to facilitate the evaporation of the solvent. If the
vacuum desiccator (B) is used, the watch-glass should always be
covered with a second inverted glass, otherwise, unless the air is
subsequently admitted very carefully, the sudden draught may
sweep the finer crystals off the watch-glass: moreover, the
inverted watch-glass will protect the crystals if, during the
evacuation of the desiccator, the pump should for any reason
cease working and so allow a mixture of air and water to rush back
into the desiccator. As a further safeguard, a Buchner flask
arranged as a trap (as K in Fig. 14, p. 31) should always be fitted
between the desiccator and the pump.
(4) Checking the Purification. The purity of the dry re-
crystallised material must now be determined, as it is possible
that repeated recrystallisation may be necessary to obtain the
pure material. The purity is therefore checked by a melting-
point determination, and the recrystallisation must be repeated
until a sharp melting-point is obtained. Should the compound
have no well-defined melting-point (e.g., the salt of an organic
acid or base), it must be analysed for one suitable component
element, until its analysis agrees closely with that theoretically
required.
METHODS AND MANIPULATION 21
Experiment 4. Choice of Solvent and Complete Re-
crystallisation. Students should be supplied with distilled
water and with the more common organic solvents, and also with
the compounds mentioned below. Taking each compound in
turn they should decide, by the methods described in (i) above,
which of these six solvents is the best for recrystallisation. They
should then recrystallise about 5 g. of at least two of the com-
pounds, dry the product, and whenever possible take its melting-
point.
Naphthalene, oxalic acid (hydrated), cinnamic acid, acetamide,
benzamide, m-dinitrobenzene, p-nitrophenol, toluene p-sulphon-
amide.
Students should appreciate that this is probably the most
important experimental work (for their purpose) described in
this book, and it should therefore be performed with great care.
Moreover, on subsequent occasions in the laboratory when short
periods are available, e.g.y during the longer stages of a prepara-
tion, they can put this time to valuable use by taking small
quantities of organic reagents from the side-shelves, and prac-
tising for themselves the process of selecting (on a test-tube
scale) a suitable solvent for recrystallisation.
Decolorisation by Animal Charcoal.* It sometimes hap-
pens (particularly with aromatic and heterocyclic compounds)
that a crude product may contain a coloured impurity, which on
recrystallisation dissolves in the boiling solvent, but is then partly
occluded by crystals as they form and grow in the cooling solution.
Sometimes a very tenacious occlusion may thus occur, and
repeated and very wasteful recrystallisation may be necessary to
eliminate the impurity. Moreover, the amount of the impurity
present may be so small that the melting-point and analytical
values of the compound are not sensibly affected, yet the appear-
ance of the sample is ruined. Such impurities can usually be
readily removed by boiling the substance in solution with a small
quantity of finely powdered animal charcoal for a short time, and
then filtering the solution while hot. The animal charcoal
adsorbs the coloured impurity, and the filtrate is usually almost
free from extraneous colour and deposits therefore pure crystals.
This decolorisation by animal charcoal occurs most readily
in aqueous solution, but can be performed in almost any organic
solvent. Care should be taken not to use an excessive quantity
* Sometimes termed activated or decolorising charcoal, to distinguish it
from wood charcoal, which absorbs gases.
22 PRACTICAL ORGANIC CHEMISTRY
of charcoal, however, as it tends to adsorb some of the solute as
well as .the coloured impurity.
Students should distinguish carefully between the animal charcoal
used for decolorisation, and the wood charcoal which is used for
absorbing easily liquefiable gases, and which is therefore used in gas
respirators and also, when chilled in liquid air, for obtaining high vacua.
Animal charcoal can usually be used as described above without any
serious risk of impurities originally present in the charcoal itself dis-
solving in the hot solvent, and then separating again with the recrys-
tallised material. To remove such risk entirely, the animal charcoal
can be boiled under reflux with dilute hydrochloric acid (i : i by
volume) for 3 hours. The mixture is then diluted with hot distilled
water, filtered through a Buchner funnel, and washed repeatedly with
much boiling distilled water until all trace of acid has been removed.
It is then well drained and finally dried by heating gently in an evapora-
ting-basin over a sand-bath until a fine dry powder is obtained.
Experiment 5. Decolorisation of Crude Sulphanilic Acid.
"Technical" sulphanilic acid is usually almost black in colour.
Place 6 g. of the crude powdered acid in each of two conical
flasks A and B (of about 200-250 ml. capacity), add ioo ml. of
distilled water to each, but add 0-5-1 g. of animal charcoal to
the flask A alone. Heat the two flasks side by side, so that the
contents boil gently for about 5 minutes and the volume of the
solutions is thus only slightly reduced. Now filter each solution
rapidly. This can be done in two ways: (a) At the pump, using
Buchner funnels and flasks which have been preheated by the
filtration of boiling distilled water. Pour the filtrates into two
beakers and allow to cool spontaneously side by side for com-
parison, (b) Through ordinary conical funnels fitted with fluted
filter-papers and preheated by the filtration of boiling distilled
water. In this case collect the filtrates directly into two conical
flasks. Crystallisation occurs rapidly. When the solutions are
cold and crystallisation complete, filter through cold Buchner
funnels. Compare carefully the colour of (i) the two hot filtrates
before crystallisation starts, (ii) the crystals when filtered and
drained. The filtrate and crystals obtained from the flask A
(using charcoal) should be colourless, whereas those from B
will both retain a deep brown colour.
A similar experiment can be performed with commercial
aniline hydrochlonde (or "aniline salt").
Animal charcoal has a further use. Occasionally, when recrystallising
a crude product, it is found that the hot solutior contains a very fine
suspension of an insoluble impurity. This suspension may be so fine
that, although apparent to the eye, it passes freely through the usual
METHODS AND MANIPULATION 23
filter-paper (particularly when a Buchner funnel is used), and thus
cannot easily be eliminated. Alternatively the suspension may be
easily held back by the filter-paper in the Buchner funnel, but then
may rapidly block up the pores of the filter and so arrest filtration
almost completely, with the result that crystallisation occurs in the
cooling solution while it is still in the Buchner funnel, i.e., before
filtration is complete. Both these difficulties can usually be overcome
by boiling the solution with a small quantity of animal charcoal. The
latter readily adsorbs such fine suspensions, and the hot solution can
then be filtered clearly and rapidly through the Buchner funnel.
Sublimation. This process is occasionally used for the
purification of solid organic compounds. Its use is necessarily
limited to those compounds which on heating pass readily and
directly from the solid to the vapour state, with a subsequent
ready reversal of this process when the vapour is cooled. A simple
form of apparatus which gives good results is shown in Fig. 10.
The dry crude material is placed in a small evaporating-basin A,
which is placed on a wire gauze. A is then covered with a filter-
paper B which is pierced by a number of small holes (about 2
mm. in diameter), made in an upward direc-
tion. A glass funnel C, the rim of which is
rather smaller than the largest diameter of A,
is then inverted as shown over the paper B.
The basin A is then gently heated by a small
Bunsen flame, which should be carefully pro-
tected from side draughts by screens, so that
the material in A receives a steady uniform
supply of heat. The material vaporises, and
the vapour passes up through the holes into
the cold funnel C. Here it cools and condenses FlG I0
as fine crystals on the upper surface of the
paper B and on the walls of C. When almost the whole of the
material in A has vaporised, the heating is stopped and the pure
sublimed material collected. In using such an apparatus, it is
clearly necessary to adjust the supply of heat so that the crude
material in A is being steadily vaporised, while the funnel C
does not become more than luke-warm.
For an example of sublimation, see the preparation of anthra-
quinone, p. 259: for semi-micro sublimation, see p. 69.
Purification of Liquid Substances.
The purification of liquids is almost invariably performed by
distillation, and the type of distillation employed will depend
largely on the nature of the impurities and in particular whether
24 PRACTICAL ORGANIC CHEMISTRY
they are volatile or non-volatile. The commonest impurity in
liquid compounds, namely water, should however be removed
before distillation whenever conveniently possible.

Drying of Liquid Compounds.


Liquids are almost invariably dried by being kept in contact
with a suitable powdered solid dehydrating agent, the dehydration
being occasionally facilitated by boiling the liquid gently under
reflux. When dehydration is complete, the liquid is either de-
canted or (better) filtered from the dehydrating agent, and can
then at once be further purified by distillation. The commonest
dehydrating agents, with their practical limitations, are:
Calcium chloride Cannot be used for alcohols, phenols or amines,
(granular). with all of which it combines. Not advisable
for acidic liquids, as ordinary calcium chloride
always contains some calcium hydroxide
owing to partial hydrolysis during preparation.
Calcium oxide Usually used for alcohols (see p. 88). Cannot
(quicklime). be used for acidic compounds, nor for esters,
which it would hydrolyse.
Potassium hydroxide. Particularly suitable for amines. Obviously
cannot be used for any liquids affected by
alkalis, e.g., acids, phenols, esters.
Potassium carbonate. Sometimes used in place of potassium hy-
droxide for amines, etc., when a strongly alka-
line drying agent is to be avoided.
Sodium sulphate (pow- Can be used on almost all occasions, but its
dered anhydrous). dehydrating action is rather slow.
Magnesium sulphate A neutral drying agent, which, like sodium
(powdered anhy- sulphate, can be used on most occasions. Its
drous). drying action is more rapid than that of sodium
sulphate.
Calcium sulphate Applicable to all liquids.
("Drierite").
Metallic sodium Used particularly for ethers. Cannot be used
(preferably as wire). for any compound affected by alkalis, or easily
subject to reduction (owing to the hydrogen
evolved during dehydration).
Liquids are occasionally purified by removing impurities as
constant-boiling mixtures, or by shaking with concentrated
sulphuric acid and subsequently separating the dried liquid from
the acid: the second method is therefore limited to liquids which
are insoluble in, and chemically unaffected by, the strong acid
(e.£., benzene, anhydrous chloral).
METHODS AND MANIPULATION 25
Distillation. If the impurities in a liquid are non-volatile,
the liquid may be purified by direct distillation, the impurities
remaining in the distilling-flask. This process is therefore
essentially the same as a simple distillation for boiling-point
determination, and has been already described on pp. 7-9.
If, however, the impurities are themselves volatile liquids, then
the separation of these impurities from the main bulk of the
required substance is achieved by fractional distillation. If an
ordinary distilling-flask, such as that shown in Fig. 2, p. 8, is
used for this purpose, however, only a very partial separation of
the liquid components of the crude mixture is usually obtained,
unless there is a considerable difference in boiling-point between
the impurities and the main component. To obtain a much sharper
and more complete separation, a fractionating column is em-
ployed.

Fractional Distillation. For this type of distillation, the


fractionating column is inserted vertically between the flask
containing the boiling liquid and the condenser. The principle
of a fractionating column is that, as the vapours ascend the
column from the boiling mixture below, the higher-boiling
components are condensed and returned to the flask, the ascending
column of vapour being thus steadily " scrubbed " by the descend-
ing column of liquid condensate. The ascending column of
vapour becomes therefore steadily richer in the lowest-boiling
component, and the descending column of condensate steadily
richer in the highest-boiling component. It follows that the
prime factor which determines the efficiency of a column is the
extent to which the vapour is " scrubbed " by the condensate, and
columns are therefore designed to make this "scrubbing" as
intimate as possible. Text-books of theoretical organic chemistry
frequently illustrate remarkable and weird types of fractionating
column which the practical chemist never encounters. For
actual use in the laboratory two types of column are recommended.
(A) For quick rough separations, or (more particularly) for the
separation of two components having a considerable difference in
boiling-point, the pear column (Fig. U(A)) is useful. The
increase in cooling surface produced by pear-shaped bulbs
causes considerable condensation, and the condensate, steadily
dripping down from the lower shoulder of each bulb, comes in
moderate contact with the ascending vapour. The efficiency of a
column can, of course, be increased by increasing the number of
bulbs in the column. (B) For accurate work, the column shown
26 PRACTICAL ORGANIC CHEMISTRY
in Fig. U(B) is probably the most efficient and generally useful
type available in most laboratories. It consists of a simple glass
column, packed with very short sections of glass tubing, the bore
of these sections preferably decreasing steadily up the column.
For general purposes, the column itself should be about 11-12 mm.
internal diameter, and the glass sections* towards the bottom of
the column should be about 5 mm. long and 6 mm. external
diameter, and towards the top about 3 mm. long and 5 mm,
diameter: the length of the column actually packed with the
tubes should be about 20 cm., but for low-boiling mixtures this
length of the column may be considerably increased, and for high-
boiling mixtures correspondingly decreased. To retain the glass
tubes in position, it is inadvisable to constrict the column immedi-
ately below the tube, as this readily causes "choking" of the
column when in use. It is better either to seal across the inside
of the column a very fine glass rod, on which the tubes may rest,
or (more easily) to have one section of glass tubing rather larger
than the rest at the bottom of the column and to fix this per-
manently in place by fusing it
carefully to the wall of the
column. The sections must be
arranged as irregularly as pos-
sible in the column: if they
tend to arrange themselves
regularly they should be well
shaken up, otherwise " chan-
nelling " of the condensed
liquid will occur and the effici-
ency of the column will be de-
creased. These sections of
glass tubing are preferable to
similar sections of metal for
(A) two reasons, (a) the metal sec-
tions, because of their low
specific heat, do not condense
sufficient of the ascending
vapour, and the efficiency of
the column falls considerably
in consequence; (b) if the tube
p1G u becomes fouled in use, parti-
cularly by traces of tarry pro-
* These glass sections for fractionating columns may he purchased from
Messrs. Quickfit & Quartz, Ltd., Quickfit Works, Stone,"Staffs, STl5 OBG.
METHODS AND MANIPULATION 27
ducts, it can always be cleaned by pouring acids, dichromate
mixture, etc., down the column, or even by being allowed to
stand overnight immersed in such cleaning agents. For the
fractionation of high-boiling liquids it is advisable to have a
kgging of cotton-wool D around the column as shown.
To use such a column, the crude liquid is placed in a round-
bottomed flask C having a short wide neck, the usual fragments of
unglazed porcelain are added, and the column then fixed in
position, great care being taken to ensure that it is mounted
absolutely vertically, again in order to avoid channelling. A
water-condenser is then fitted in turn to the side-arm of the
column, particularly when the components of the mixture have
low boiling-points. The mixture is then heated with a very
small flame, carefully protected from draughts to ensure a uniform
supply of heat. It is essential that the initial heating of the
liquid in C (while it is still mounting the cold column) should not
be hurried, as considerable extra condensation occurs while the
column is warming up, and the latter may easily choke: when
once distillation has started, and a thermal equilibrium has been
established between the column and its surroundings, the ten-
dency to choke should disappear. The heating is then adjusted
until the distillate is issuing from the side-arm of the column not
faster than about i drop every 4-5 seconds. In these circum-
stances, so efficient a fractionation should be obtained that, when
the lowest-boiling fraction has distilled over, distillation com-
pletely ceases, as the next lower fraction is refluxing definitely
below the side-arm of the column. The heating is then cautiously
increased, and a sharp rise in boiling-point (and therefore a sharp
fractionation) should occur as the second fraction starts to distil.
Although in Fig. IZ(B) a condenser is shown fitted to the side-
arm of the column, this is required only for low-boiling com-
ponents: for most mixtures, however, the above rate of distilla-
tion, necessary for efficient fractionation, will be accompanied
by complete condensation in the side-arm of the column, from
which the successive fractions may be collected directly.
In using a column of this type, it is essential that the distillation
be not hurried. Although the complete fractionation may
therefore take a moderate time, yet the fractionation is so efficient
that the over-all time for the complete process is very much less
than when more rapid columns are used, for in the latter case the
fractionation usually has to be repeated several times in order to
obtain as complete a result.
28 PRACTICAL ORGANIC CHEMISTRY
Experiment 6. Fractional Distillation of a Mixture
of Benzene and Toluene. Fractionally distil about 40 ml. of
a mixture of equal volumes of benzene and toluene, using the
type of fractionating column shown in Fig. i I(B), in which about
18-20 cm. of the column are actually filled with glass sections,
but in which the cotton-wool lagging is not used. Distil very
slowly, so that the total distillation occupies about i£ hours.
Shield the apparatus very carefully from draughts. Collect the
fractions having the b.ps (a) 80-85°, (^) 85-107°, (c] 107-111°.
A sharp separation should be obtained, e.g., these fractions should
have volumes of about 19, 2, and 17 ml. respectively.
It will be found that the first few drops of the lowest fraction
are always cloudy, owing mainly to the fine film of water adsorbed
on the glass surfaces within the column.
Distillation under Reduced Pressure. Occasionally a
liquid, when distillation is attempted under atmospheric pressure,
will undergo partial or complete decomposition before its boiling-
point is reached. To overcome this difficulty, the liquid is dis-
tilled under reduced pressure, so that its boiling-point shall be
definitely below its thermal decomposition point.
It has already been pointed out that a liquid even when sub-
jected to simple atmospheric distillation may become superheated
and then "bump" violently in consequence: this danger is
greatly increased during distillation under reduced pressure and
therefore a specially designed flask, known as a Claisen flask, is
used to decrease the risk of superheating. In Fig. 12(A) a
Claisen flask D is shown, fitted up as part of one of the simplest
types of vacuum-distillation apparatus.*
The flask has two necks, the right-hand one carrying a ther-
mometer in the usual way, while the left-hand one carries a stout
capillary tube E, which is closed at the top by a short piece of
pressure tubing and a screw-clip, by which the amount of air
passing through the capillary can be regulated. The capillary
tube E should always be prepared by drawing out a piece of thick-
walled capillary tube of about 4-5 mm. external bore, and then
adjusting the length of the fine capillary tube below so that it
reaches to within 1-2 mm. of the bottom of the flask: it should
never be prepared by drawing out an ordinary glass "quill" tube,
otherwise the fine capillary so obtained will be too fragile, and will
probably snap during the course of the distillation. The side-
* For all vacuum distillations, a trap (cf. K, Fig. 14, p. 31) should be fitted
near the pump, in case the water "sucks back".
METHODS AND MANIPULATION 29

(A)

arm is then fitted to an ordinary distillation-flask F, which serves


as a receiver for the distillate. Well-bored rubber stoppers
should be used throughout the apparatus, and immediately before
being inserted in position should be lightly smeared with a solu-
tion of good-quality rubber in benzene to ensure an air-tight
fit. (For a ground-glass distilling flask similar to D, see Fig. 23(F),
p. 46-)
Before performing a distillation, the flask D is filled not more
than half-full with the liquid, some fragments of porcelain] added,
and the capillary, thermometer and receiver then placed in
position, the side-arm of the receiver F being connected through a
manometer to an efficient water-pump. As the pressure falls to
a steady value, the screw-clip above the capillary E is adjusted
until a steady stream of fine bubbles is emerging through the
lower end of E. If it is anticipated that the liquid will boil
below about 100°, the whole of the bulb of the receiver F is
cooled with a stream of water as shown, the waste being collected
by a funnel below and run off to the sink. In most cases, how-
ever, it is sufficient to have the bulb of F dipping into a basin of
ice-water. A water-condenser is not necessary with this appara-
tus if the distillation is carried out slowly. The liquid in D is then
heated steadily, preferably in an oil-bath, and in these circum-
stances steady ebullition should occur: the temperatu-e of the
vapour and the pressure in the apparatus, indicated by the
thermometer and the manometer respectively, should then be
read.
f Or carborundum nodules, cf. p. 8.
30 PRACTICAL ORGANIC CHEMISTRY
Examples of the use of this apparatus (or that shown in Fig. 14, p. 31) will be
found in the preparation of phenylhydrazine (p. 195), ethyl acetoacetate (p. 264),
ethyl malonate (p. 272), quinaldine (p. 300), triethyl phosphite (p. 308) and
di-isopropyl hydrogen phosphite (p. 309).

The simplest form of manometer for this purpose is an ordinary


barometer tube, as shown in Fig. IZ(B): this form has the
disadvantages, however, that the surface of the mercury in the
tube is easily fouled and then difficult to read, and that in any
case an accurate measurement of the long column of mercury is
not simple.* A neater and more accurate type of manometer is
shown in Fig. IZ(G). The mercury is contained in a fine glass
U-tube G fused to a horizontal cross-piece, which is sealed on
one side, and on the other leads through the tap I to a thick-walled
U-tube H, which contains granular calcium chloride in the left-
hand arm, and soda-lime in the right-hand arm, the reagents
being kept in position by the three plugs of glass wool P. To
prevent fouling of the mercury surface, the manometer should be
placed not directly in line between the distillation apparatus and
the pump as in (B), but as a " side-arm" between these two.
With this precaution, and with the additional protection by the
reagents in H, the mercury surface should with care remain clean
for years.
When constructing a manometer of the type shown in Fig. iz(c), it is impor-
tant to apply a very high vacuum (e.g., with a Hy-Vac pump) to the manometer
while the mercury in the left-hand (sealed) limb is heated until it boils: unless
this is done, traces of air will remain in this limb and cause inaccurate readings.
During a distillation, the tap I should be kept closed except when a pressure
reading is being taken: if it is left open indefinitely, a sudden default by the
distillation apparatus or by the pump may cause the mercury in the sealed limb of
G to fly back and fracture the top of the limb.
Other similar types of manometer, usually reading over a range of about 10-60
mm., are available in many laboratories.

Fractional Distillation under Reduced Pressure. One great


disadvantage of the simple vacuum-distillation apparatus shown in
Fig. IS(A) is that, if more than one fraction distils, the whole process
has to be stopped after collecting each consecutive fraction, in order to
change the receiver F. This may be overcome by replacing the simple
receiving flask F by a "pig" (Fig. 13) which collects consecutive

* Furthermore, the open exposure of mercury in any apparatus, particularly


one in frequent use, is to be avoided, as even at room temperature the mercury
gives appreciable quantity of the toxic vapour.
METHODS AND MANIPULATION
To pump
fractions without interruption of the
distillation. The "pig" consists of a
stout glass receiver A, which fits either
over the side-arm of the Claisen flask
or, in the case of low-boiling liquids,
over the end of the condenser which is
fitted to this side-arm. It has at the top
an outlet tube B for connection to the
manometer and pump, and at the lower
end usually three outlet tubes to which
FIG. 13. are fitted consecutive receivers C, D, E.
When distillation starts, the "pig" is
so placed that the first fraction collects in C. When the second fraction
starts to distil, A is rotated slightly to bring the outlet tube leading to
D in the lowest position, so that the second fraction collects in D:
further rotation then causes the third fraction to collect in E. The
apparatus however often gives unsatisfactory results, particularly in the
hands of students, who frequently find that if a good vacuum is obtained
in the apparatus, the "pig" sticks firmly around the cork F and refuses
to rotate: conversely, easy rotation around this cork usually means a
leaky joint at this point, and an unsatisfactory and varying pressure is
recorded by the manometer. (The ground-glass fitting B shown in
Fig. 23(p), p. 46, avoids this trouble.)
For general work, a very satisfactory apparatus for collecting
fractions under reduced pressure is the Perkin triangle C,* which is
shown in Fig. 14, together with the requisite fittings for the complete

To pump

FIG. 14.

* G. A. R. Kon (your. Chem. Soc., 1930, 182) described a modification


of the Perkin triangle having only two taps instead of the three described
above. It may be purchased from Quickfit & Quartz, Ltd., Quickfit Works,
Stone, Staffs.
32 PRACTICAL ORGANIC CHEMISTRY
distillation. A is a Claisen flask, fitted up as already described, and
heated in a beaker of transparent medicinal paraffin, the temperature
of which is carefully controlled throughout the distillation.
The Claisen flask is then fitted to a water-condenser B, which leads
directly into the main receiver C of the triangle. This triangle is
connected through the upper tap D to the manometer and pump, and
by the lower tap E to a supplementary (bottle) receiver F. The tube
leading from E to the receiver F is double-walled: the inner tube
gives direct access from C through the tap E to the receiver F, while
the outer (annular) tube provides access from F through the small
holes H to the side-arm JJ' carrying the three-way tap G. G is made to
give either direct access through the tube JJ', or access from the outside
through J downwards to F, or from the outside through J' to the mano-
meter and pump. The triangle is then connected to the manometer
(fitted in a "side-chain'* as before) and through the trap K (a Buchner
flask) to the pump. The function of K is to "smooth out" slight
changes in the pressure, within the apparatus, and also, should the pump
default, to prevent water from rushing back into the apparatus.
When distillation starts, the taps D and E are open, and G is turned
so as to give direct access from J to J'. The first fraction therefore runs
from C through E, and collects in F. Directly the second fraction
starts to distil, E is closed, so that this fraction collects in C. Meanwhile
G is turned to allow air to enter through J to F, which can then be
detached and a new receiver F' added. If a pump of good capacity is
being used, it is sufficient now to turn G so as to give direct access
again between J and J', thus evacuating the new receiver F', which is
then ready to receive the second fraction which has been accumulating
in C. If a rather weak pump is in use, however, this sudden admission
of the air from the new receiver F' into the rest of the apparatus may
cause a moderate rise in the pressure, and a temporary cessation in the
distillation, and in these circumstances "bumping" frequently starts
(and persists) when distillation recommences. To avoid this, the tap
G, before being turned, should be connected to a supplementary pump,
which will evacuate the new receiver F': rotation of G as before now
serves to cut off the supplementary pump and simultaneously reconnect
the two parts of the apparatus through JJ'.
When a more delicate fractional vacuum-distillation is required, the
flask and column shown in Fig. U(B), p. 26, may be used, the side-arm
of the column being fitted directly into receiver C (Fig. 14). A rubber
stopper must then be used to fit the flask on to the fractionating column,
and it should also carry a capillary tube leading to the bottom of the
flask, to provide the usual fine stream of bubbles to prevent bumping.

Steam-distillation. Many water-insoluble compounds, both


solid and liquid, may be readily purified by distillation in a
METHODS AND MANIPULATION 33

(A)
FIG. 15.

current of steam, provided that the compound is volatile, and the


impurities non-volatile, under these conditions.
The apparatus consists of a round-bottomed flask C (Fig. 15
(A)), having a glass inlet tube which reaches almost to the bottom
of the flask and which is connected to a steam generator D: the
flask C has also a glass outlet tube, connected in turn to the water-
condenser E. The flask is clamped at an angle as shown to
prevent the solution in C from being splashed into the entrance
of the outlet tube and thus being blown over mechanically into
the condenser: this purpose is achieved more completely if in
addition a still-head (shown on a larger scale in Fig. IS(B)) is
used in place of the outlet tube, since spray will be trapped in
the still-head, and returned as a steady stream of liquid to the
flask C. (A ground-glass unit combining the steam-inlet and the
still-head is shown in Fig. 22(1), p. 43.)
The material to be steam-distilled (mixed with some water if
a solid compound, but not otherwise) is placed in C, and a
vigorous current of steam blown in from D. The mixture in C
is thus rapidly heated, and the vapour of the organic compound
mixed with steam passes over and is condensed in E. For
distillations on a small scale it is not necessary to heat C: if,
however, the flask C contains a large volume of material or
material which requires prolonged distillation, it should be heated
by a Bunsen burner, otherwise the steady condensation of steam
in C will produce too great a volume of liquid.
34 PRACTICAL ORGANIC CHEMISTRY
If the organic compound which is being steam-distilled is freely
soluble in water, an aqueous solution will ultimately collect in the
receiver F, and the compound must then be isolated by ether
extraction, etc. Alternatively, a water-insoluble compound, if
liquid, will form a separate layer in F, or if solid, will probably
crystallise in the aqueous distillate. When steam-distilling a
solid product, it is sometimes found that the distilled material
crystallises in E, and may tend to choke up the condenser: in
such cases, the water should be run out of the condenser for a
few minutes until the solid material has melted and been carried
by the steam down into the receiver.

Experiment 7. Steam-distillation.
Students should carry out the purification by steam distillation
of (a) crude nitrobenzene or chlorobenzene, or of (b) crude
naphthalene, o-nitrophenol (p. 170) or p-tolunitrile (p. 194) as
examples of solid compounds which may also be purified in this
way. When the distillation is complete, disconnect the tubing
(Fig. 15) between C and D be/ore removing the flame from under
D, otherwise the contents of C will be sucked back into D as the
latter cools.

Ether Extraction. In the course of organic preparations, it


frequently happens that an organic compound is obtained either
in aqueous solution or (less often) in aqueous suspension; if the
organic compound is volatile in steam, or if it is chemically
affected by prolonged exposure to hot water, it clearly cannot be
isolated by evaporation of the water. If, however, the compound
is soluble in an organic solvent which is itself almost completely
insoluble in water, then repeated extraction of the aqueous
solution with the solvent will eventually transfer the compound
almost entirely into the organic solvent. Any water-insoluble
solvent may be used for this purpose, but ether is usually the
most suitable because (a) it is chemically inert and is unlikely to
react with the compound, (b) owing to its great volatility, it can
subsequently be readily removed by distillation without serious
risk of simultaneously volatilising the compound.
To extract the substance, the aqueous solution or suspension
is placed in a separating-funnel, which may be either cylindrical,
Fig. i6(A), or (better) pear-shaped, Fig. i6(B). Ether is then
METHODS AND MANIPULATION 35
added and the mixture thoroughly
\s shaken, the stopper at the top of
fj the cylinder being occasionally
^x^~^\ opened to relieve any pressure of
ether vapour caused by the heat of
the hands. The mixture is allowed
to settle until two well-defined
layers have formed, and the lower
aqueous layer is then run off and
separated as completely as pos-
sible. The remaining ethereal
layer is run off, preferably by
pouring it through the upper neck
of the funnel, to avoid contamina-
tion with any drops of aqueous
solution still remaining in the stem
(A) (B) of the funnel below the tap. The
FIG. 16. aqueous solution is then returned
to the funnel, and the extraction
repeated, using fresh ether on each occasion, until it is judged
that very little of the compound remains in the aqueous layer. It
should be borne in mind, however, that if a given volume of ether
is to be used for the complete extraction, a far more efficient
result will be obtained by a number of consecutive extractions
using only a small volume of ether for each extraction, than by
one or two extractions using a correspondingly greater volume of
ether each time.
The ethereal extracts are then united, dried with a suitable
drying agent and filtered. The filtrate is then cautiously distilled,
the ether being first distilled and finally the organic compound
if volatile: if the compound is solid, the crude residue is puri-
fied by recrystallisation. Very great care must be taken on all
occasions when ether is distilled, because of the risk of fire or of
an explosion: full experimental details for this operation are
given, both on p. 80 (Preparation of Ether) and on p. 164 (Pre-
paration of Aniline).

Continuous ether extraction and continuous chloroform


extraction. When a substance X is shaken up with ether and water
it will distribute itself according to the relative solubilities in each
solvent.
^, _„ , .. rr - ^ Cone, in ether layer
Thus K (partition
vr coefficient) = ~ -. £
Cone, in aqueous layer
36 PRACTICAL ORGANIC CHEMISTRY
Now if K is very small, the amount of X going into the ether layer will
also be very small and it would be quite impracticable to carry out
more than three or four extractions. This difficulty can, however, be
easily overcome by employing continuous ether extraction using the
apparatus shown in Fig. 17 (A).

The ether is placed in the flask E. The aqueous solution is placed


in the wide tube A. On heating E, ether vapour passes up the side-tube
B to the condenser C, from whence liquid ether falls through the
central vertical tube D to the bottom of the aqueous layer in A. Small
drops of ether ascend through the aqueous layer, and in so doing expose
a relatively large surface and extract some of the solute. The ethereal
extract gradually increases in bulk, and the upper part of it is returned
continuously by the system F to the flask E. Here the ether is again
vapourised and recycled as above. Thus after a large number of cycles
the solute will gradually accumulate in the ether in E and the solute can
then be recovered by normal distillation or evaporation of the ethereal
solution.
A convenient alternative apparatus for continuous ether extraction
is shown in Fig. 17 (B).
METHODS AND MANIPULATION 37
The two forms of apparatus, Fig. 17 (A) and (B), are suitable for any
solvent immiscible in and lighter than water. Fig. 18 (A) shows an

FIG. 18.

apparatus suitable for continuous extraction of aqueous solutions with


solvents heavier than water (e.g., chloroform). In this case chloroform
is placed in the flask E, and the aqueous solution in tube A. The
chloroform is boiled and its vapour ascends the tube B, is condensed
and then falls in droplets through the aqueous phase in A. When the
lower chloroform layer reaches a certain height much of it will siphon
through F back into E. From here the solvent is recycled, and gradu-
ally the chloroform in E becomes more concentrated with respect to
the solute.
A convenient alternative apparatus for continuous chloroform extrac-
tion is shown in Fig. 18 (B).

Soxhlet Extraction. Occasionally a crude product (often of


natural occurrence) is obtained, from which a particular component
may be isolated by repeated extraction with a hot solvent. For this
purpose, Soxhlet's Extraction Apparatus (Fig. 19) is usually employed.
38 PRACTICAL ORGANIC CHEMISTRY
The extractor consists of a glass cylinder A, terminating
at the base in the open tube B. Fused within the top of A
as shown is another tube C, having a small hole D blowrn
in the side: a fine glass tube leads from the base of C,
rises about two-thirds of the height of the cylinder to E,
and then returns past F into the open tube B. /
The crude organic material is placed in a porous thimble
G (made of tough filter-paper), and the latter placed as
shown within the inner tube C. The apparatus is then
fitted below to a bolt-head flask H containing the requisite
solvent, and above to a reflux water-condenser J.
The solvent in H is then gently boiled. The vapour
passes up B, through the annular space between the tubes
C and A, and so through the orifice D into the reflux
condenser above. The condensed solvent falls down into
the thimble G, and slowly fills the body of C, being
meanwhile heated by the ascending mantle of hot vapour
in the annular space outside. When this condensed liquid
reaches the top E of the fine glass tube, it syphons down
into the flask H, taking down that portion of the organic
compound which it has extracted in G. The process then
repeats itself indefinitely, more of the organic material
being extracted from G and transferred to the solvent in H
on each occasion. Eventually complete extraction of the
crude product in G is effected, and the extracted com-
pound can then be isolated from the solution in H by any
of the usual methods.
H ^
NOTE. In the older types of Soxhlet extractor, an ex- FIG. 19.
ternal tube ran from B up to the top of C for conveying
the ascending column of hot vapour. This type had the disadvantage
not only of being more easily broken, but also that the condensed liquid
in C received very little heat, and therefore the extraction, being carried
out by the lukewarm solvent, was usually very slow.

Stirring. In the course of many organic preparations, a


solution or suspension has to be kept continuously agitated either
during the addition of a reagent or throughout the main stage of
the preparation. For other than small-scale preparations>
mechanical stirring is most conveniently employed. For this
purpose, a stirrer S (Fig. 20) is made of stout glass rod, with the
lower end bent at right angles if it is intended to sweep over the
flat base of a beaker, or curved (as shown in Fig. 20) if it is to be
used inside a round-bottomed flask. Other types can be designed
for special purposes, or to allow insertion within a narrow-
necked flask. The stirrer may be connected to an electric motor
METHODS AND MANIPULATION 39
by a pulley P, which is particularly useful if a number of stirrers
are run off one revolving shaft. It is usually more convenient,
however, to secure the stirrer S directly to the axis of a small
motor, which is therefore clamped perpendicularly above.
mA
JT

\ I
FIG. 20.
It is frequently necessary, however, to stir a solution which
is boiling under reflux, and the stirrer must therefore be fitted
with a seal to prevent the escape of vapour. This can often be
done very simply by means of a short glass tube T (Fig. 20)
which passes through the cork of the flask, and which serves as a
collar within which the stirrer A fits quite closely. To prevent
the escape of vapour, a short length of rubber tubing R (about
11 inches long) is fitted over the top of the tube T: the upper
portion of this tube is then turned back over the stirrer as shown
in order to grip the stirrer securely. A few drops of glycerol or
mineral oil placed between the upper portion of this tubing and
the stirrer allow the latter to rotate freely with very little friction.
Alternatively a mercury-sealed stirrer may be employed. Here
again a short glass tube C is inserted through the cork of the
flask to act as a collar for the stirrer. The tube C carries a
short wide tube B which is either fused at its lower end to C, or
is fixed to it by means of a cork as shown. The stirrer D carries
a precisely similar tube E, the top of which however is now
fixed to D: the bore of the tube E allows it to fit easily within
the annular space between the collar C and the tube B. Mercury
4o PRACTICAL ORGANIC CHEMISTRY
is then placed in this annular space to act as a seal whilst the
stirrer is in operation.

Assembling Apparatus. The following points should be


noted.
(1) Drying Apparatus. Simple pieces of apparatus such as
flasks are best dried by heating in the large luminous flame of a
blowpipe, a current of air, e.g., from compressed air mains,
being blown through the flask meanwhile to remove the water
vapour, which would otherwise merely recondense as the
flask cooled. Apparatus such as condensers, etc., which cannot
be so treated, should first be rinsed out with methylated spirit,
and then with ether (preferably dried beforehand over calcium
chloride and filtered): a brisk current of air is then blown
through the apparatus until the ether has completely evaporated.
In most laboratories, drying ovens maintained at about 50°
are available for the final drying of glass apparatus of all kinds.
(2) Corks * Before using an ordinary bark cork, examine it
carefully for flaws: many corks have such deep holes that they are
useless. Before boring, always roll the cork thoroughly (under
the foot, if a cork-roller is not available) in order to soften it.
Never bore a cork right through from one end to another, as the
cork-borer on emerging will almost invariably tear the surface of
the cork. Therefore bore halfway through from one end, and
then start again from the opposite end, rotating the cork steadily
each time to ensure that the borer goes symmetrically along the
long axis of the cork. With care the two borings should meet
exactly.
Never use unprotected bark corks for an apparatus in which
a carefully dried liquid is to be distilled, etc., as these corks
always contain appreciable quantities of water, which is exuded
when the cork comes into contact with a hot liquid. Rubber
stoppers should therefore be used in these circumstances.
When boring rubber stoppers, lubricate the borer well, either
with aqueous glycerine or with vaseline. Then clean well and
dry before using.

Storage of Specimens. Solid compounds after purification


should be stored in bottles or in corked specimen tubes, according
* For most purposes, the use of corks is now replaced by that of ground-
glass apparatus (p. 42 et seq.).
METHODS AND MANIPULATION 41
to the amount of the compound available. The bottle or tube
should at once be labelled, so that the identity of the compound,
its melting-point, and any particular details concerning the
method of purification employed, are clearly recorded. The
label should also record the "tare" (i.e., the weight) of the empty
bottle or tube, including that of the stopper or cork, so that the
total weight of material available can subsequently be determined
without removing the substance from the bottle. Stable liquids
of high boiling-point can be similarly stored in stoppered bottles
or in corked specimen tubes: in the latter case, however, unless
the liquid is required again shortly, it is advisable to wax the cork
in order to hold it firmly in position and also to prevent the liquid
from slowly seeping through the cork itself. For this purpose,
the cork should be placed firmly in position, and the inverted
tube dipped into some clean paraffin wax which has been heated
in an evaporating-basin to about 180°, i.e.,
until it has become a mobile liquid. After the
cork and the extreme end of the tube have
been immersed in the wax, the tube is removed
and, while still inverted, gently rotated so
that the wax solidifies as a layer of uniform
thickness.
The only satisfactory method for storing
liquids of low boiling-point (e.g., ethyl
bromide) or liquids which are affected by the
air (e.g., acetic anhydride, benzoyl chloride,
benzaldehyde) is to seal them in special glass
bottles A (Fig. 21) or tubes B according to
the amount available. The bottles, of various
sizes, can be purchased: the tubes should be
prepared in the laboratory from moderately
thick-walled glass tubing. The bottle or tube
should first be cleaned and dried: then, by
FIG. 21. carefully rotating the neck in a suitable small
blowpipe flame, a constriction a (Fig. 21) of
about 15-20 mm. length should be made so that the wall of
the tubing remains uniformly thick at this point. A test-tube is
then drawn out at the centre so that the upper part can be broken
off and used as the funnel F; the liquid can now be easily poured
into A or B. If the liquid is readily volatile, the bottle or tube
must now be placed in ice-water or in ice-salt for several minutes.
It is then removed, the lower portion wrapped in a duster to
protect the liquid from the heat of the hand, and the neck
42 PRACTICAL ORGANIC CHEMISTRY
quickly sealed off at a. For liquids of high boiling-point, these
precautions are not necessary, although in all cases the constric-
tion a facilitates the sealing of the neck.
Students frequently attempt to seal liquids in test-tubes: the
latter are, however, usually too fragile for this purpose.
Apparatus having Ground-glass Joints.
Apparatus consisting solely of glass units interlocking by ground-
glass joints has for many purposes replaced the older cork- or rubber-
stoppered apparatus because its great advantages in use outweigh its
much greater cost.
These advantages include: (a) Speed of assembly, (b) Well-fitting
joints, as these are made to accurate standards and joints of any given
size are thus interchangeable, (c) Accurate alignment of assembly, for
the use of incorrectly bored corks is obviated, (d) Freedom from con-
tamination of liquids by cork and rubber.
The underlying principle of this apparatus is the interchangeable
conical ground-glass joint. The same "taper" of i in io in the dia-
meter is used for all joints, so that the inner unit fits the outer unit with
precision. A code is frequently used to designate the cone-size of the
joint, e.g.y from the small Bio to the large 655. The sizes of greatest
general utility are 614, 619 and 624.
Precautions: Students should carefully note the following points in
order to minimise breakages.
(1) Ensure that all the individual components in the assembly are
adequately supported when in position: the friction between contiguous
ground-glass surfaces does not provide adequate support. Therefore
always use clamps, the claws of which are lined with rubber or other
soft material. When assembling apparatus, allow some play in the
clamps until the individual parts are in position, and then secure the
position of the assembly by gently increasing the pressure of the clamps.
(2) It is often advisable to lubricate ground-glass joint surfaces with
an extremely thin film of vaseline. This applies particularly to joints
employed in assemblies for distillation under reduced pressure. For
distillations under greatly reduced pressures or at very high tempera-
tures it is essential to employ a special lubricant, e.g., silicone grease.
(3) Care must be used when employing alkalis. In these circum-
stances joints tend to stick unless a lubricant is used. In addition it is
advisable to rotate the units comprising the joint at frequent intervals.
Apparatus in which alkalis have been used should be dismantled
immediately after use.
Although apparatus employing ground-glass joints is excellent for
work on a macro scale, it is not always suitable for very small-scale
work as the joints are often disproportionately large compared with the
rest of the assembly. The semi-micro apparatus described on pp. 59-72
can therefore be considered as being of general utility for this scale of
work, especially as the use of corks has been reduced to a minimum.
METHODS AND MANIPULATION 43

(B)

(J)
FIG. 22.
Units.* Some of the chief units employed for reasonably simple ground-
glass assemblies are:
Round-bottomed flasks (Fig. 22(A)) of various sizes and having necks of various
lengths and widths. They can be closed with stoppers (Fig. 22(B)), or fitted
with any of the following units: reflux air-condensers (Fig. 22(C)) or water-
condensers (Fig. 22(D)); distillation heads, of the simple "knee-tube" type
(Fig. 22(E)), or with a vertical joint (Fig. 22(F)) for thermometers, etc., or with
* This brief account is intended to give only a general indication of the types
of apparatus available. The firm which has pioneered the design and manufac-
ture of ground-glass apparatus is Quickfit and Quartz, Ltd., "Quickfit" Works,
Stone, Staffordshire, STl5 OBG, whose catalogues fully illustrate the range of
units and assemblies available.
44 PRACTICAL ORGANIC CHEMISTRY
a double neck (Fig. 22(G)) of the Claisen type, for a capillary inlet-tube and a
thermometer; steam-splash heads, such as Fig. 22(H) and Fig. 22(1), the
latter having an additional inlet-tube for steam-distillation: adaptors having
two or three necks (Fig. 22(J)). Similar flat-bottomed flasks and conical flasks
are used when more convenient.
The above units can when required be fitted into the neck of a flask by
adaptors such as Fig. 22(K) and Fig. 22(L).
The distillation heads Fig. 22(F) and Fig. 22(G) can be fitted with
thermometers having a ground-glass cone just above the bulb (Fig. 22(M)).
These are expensive, and it is usually more convenient to fit a thermometer
pocket (Fig. 22(N)) which consists of a small "well", fitting as shown into
the neck of the flask. A small volume of mercury is placed in the well just to
cover the bulb of a conventional thermometer, and thus provides excellent
thermal contact between the thermometer and the sides of the pocket.
Capillary tubes for low-pressure distillations are prepared by drawing out
the lower end of the tube (Fig. 22(O)).
Assemblies. Other units are shown in some of the typical assemblies illus-
trated in Fig. 23.
Fig. 23(A) shows an assembly for boiling a liquid under reflux whilst adding
another liquid at a rate which can be clearly seen (cf. preparation of aceto-
phenone, p. 253). The outlet A allows expansion of the vapour content, and can
be fitted with a calcium chloride or soda-lime tube. The outlet A can also be
used for collecting a gas evolved during the reaction (cf. preparation of acetylene,
p. 88).
Fig. 23(6) shows a modification of the reflux assembly to allow a gas to be
passed through the boiling liquid (cf. Fischer-Speier esterification, p. 104). The
inlet-tube A fits into a three-necked adaptor shown in Fig. 22(J). The stopper
B can be replaced by a dropping-funnel, etc.
Fig. 23(C) shows a reflux assembly with a stirrer fitted. The stirrer A is
both held in position in the tube B and allowed to rotate freely by the lubricated
rubber sleeve C, as described on p. 39, and is connected to a vertical motor
above. The extent to which the stirrer dips into the liquid in the flask can
readily be adjusted. The condenser (not shown) is fitted into D. This con-
stitutes for many purposes the best type of stirrer. If desired, the rubber sleeve
C can be replaced by a metal fitting E for a horizontal drive. The gas-inlet F
is closed when not in use.
Fig. 23(D) shows a simple distillation apparatus with an adaptor fitted to the
lower end of the condenser. This apparatus can also be used for the recovery
of solvents, or for the concentration of a solution with collection of the distilled
solvent.
Fig. 23(E) shows a distillation assembly particularly useful for distilling
ether from an ethereal extract. When all the ether has distilled over, the drop-
ping-funnel may be replaced by a thermometer for distillation of the residual
liquid: the adaptor A and the receiver B can then be replaced by the simple
adaptor shown in Fig. 23(D) and a flask or bottle of suitable size.
Fig. 23(F) shows a similar distillation assembly for isolating a pure liquid
which is present in an organic extract and which may finally require fractional
METHODS AND MANIPULATION 45

Tube extends below bench


volatile solvents

* Water both

FIG. 23.

distillation under reduced pressure. The lower end of the condenser is fitted
with an adaptor of type A and a receiver B (Fig. 23(E)) whilst the solvent is
being distilled. For the fractional distillation of the residual liquid, the dropping-
funnel is replaced by a capillary tube, the thermometer is inserted, and then the
adaptor A (Fig. 23(E)) is replaced by a "pig" B (Fig. 23(F)) carrying suitable
receivers (of which the cylindrical and the spherical types are shown), or by an
all-glass Perkin triangle similar to that shown in Fig. 14, p. 31. If the amount
46 PRACTICAL ORGANIC CHEMISTRY

(H)

FIG. 23 (contd.).

of residual liquid is small, the distillation flask C and the still-head D can be
replaced by a small flask E (Fig. 23(F)) the neck of which can have various
fractionating devices. The ethereal extract can thus be run into E at the same
speed as the ether distils over: this process is rather slow, but the small volume
of residual liquid can then be directly distilled. The lower side-neck of E is
subsequently fitted with a capillary tube for the final distillation.
Fig. 23(G) shows a three-necked round-bottomed flask A having the two side-
METHODS AND MANIPULATION 47
arms fitted at an angle. The flask A can therefore, for example, carry through
its central neck a stirrer B and gas-inlet (closed when not in use), and through
one side-neck C a reflux condenser and through the other neck D either a
dropping-funnel or a stopper to allow intermittent additions of a solid reagent
such as sodium. For fairly large quantities of liquids, this assembly is more
robust than a single-necked flask fitted with the three-necked adaptor shown in
Fig. 22(J). The gas-inlet is particularly useful for the passage of nitrogen over
an easily oxidised liquid.
For extraction purposes, a Soxhlet apparatus (Fig. 23(H)) can be inserted
between a flask of boiling solvent and the reflux condenser A above. This
apparatus is similar in design to that shown in Fig. 19, p. 38: in the type
shown in Fig. 23(H) the hot extract continuously overflows through the side-
tube into the boiling solvent below, but the syphon type shown in Fig. 19 is also
available.
Advanced Techniques of Separation and Purification.
The methods of purification of a crude product by fractional crystal-
lisation (p. 13) and fractional distillation (p. 25) have the advantages
that they can, when required, be applied on a large scale. They have
the disadvantages that they cannot be rapidly applied to separate, for
example, two components of a crude product whose solubilities in a
range of solvents are closely similar or whose boiling-points are very
close together. Fractional crystallisation may often be impeded (or
prevented) by the formation of mixed crystals, and fractional distillation
by the formation of constant boiling-point mixtures, or by less definite
co-distillation. Purification by sublimation (p. 23) can also be per-
formed on a large scale, but its use is obviously and severely limited to
solid compounds having the necessary physical properties.
The various types of Chromatographic Separation have been deve-
loped partly to avoid the above disadvantages, but (more particularly)
to provide methods of separation on a micro-scale. Three methods are
described below:
Adsorption Chromatography
Paper Chromatography (p. 50)
Ion-exchange Chromatography (p. 55).
Thin-layer Chromatography (p. 58)

Paper Chromatography in particular frequently enables the com-


ponents of a mixture to be separated and identified when only 1-2 mg.
of the mixture are available, the process being independent of the
relative solubilities of the components.
ADSORPTION CHROMATOGRAPHY
A mixture can often be separated into its components by
utilising their selective adsorption from solution by a suitable
substance, such as active alumina: the separation can be readily
followed if the components are coloured.
The method consists essentially in allowing a solution of
the substance in a suitable solvent to pass slowly down a long
column containing the adsorbent material. The tenacity with
which this material adsorbs the various components of the
mixture may vary considerably, with the result that a sharp
separation of the components into coloured zones or bands may
result. At this stage, the passage of the solvent may be stopped
and the individual zones removed either by careful extrusion of
the adsorbent material or by cutting the tube in sections corres-
ponding with the zones. It is usually more convenient to " elute "
the components, i.e., by the further passage of the pure solvent
48
METHODS AND MANIPULATION 49
(or of a mixture of solvents) to cause each zone to pass down the
tube and ultimately to emerge as a solution of the pure com-
ponent.
If the components are colourless, their separation can often
be followed by working in a quartz (or special glass) tube which
is placed in the light of a mercury lamp. The separate zones
are then often revealed by their fluorescence.
The process of chromatographic separation is illustrated in
the following experiment, in which a wider tube than usual is
employed to give a reasonably rapid separation within the time
normally available to students. The alumina employed is the
usual active alumina as supplied by dealers.
Chromatographic Separation of a Mixture of o- and
p-Nitroaniline. Prepare a glass tube A (Fig. 24) in which the
wider portion has a diameter of 3 cm. and a length
of ca. 30 cm.: the narrow portion at the base has a
A
diameter of 5-7 mm. Wash the tube thoroughly (if
necessary, with chromic acid, followed by distilled
water and ethanol) and then dry. Insert a small plug of
cotton-wool P as shown just within the narrow neck of
the tube: it is essential that this plug does not project
into the wider portion of the tube. Clamp the tube in
a vertical position.
Mix ioo g. of active alumina with dry benzene
until a suspension or slurry of suitable consistency is
obtained, and pour this carefully into the tube. Clamp
a dropping-funnel just above the top of the tube and
allow benzene to run slowly down as the alumina
column settles in the tube: the benzene emerging from
the bottom of the tube is collected in a conical flask. It is
essential that the top of the column should be kept immersed
in the solvent, and that the latter passes uniformly down the
column without "channelling": a disc of filter-paper can, if
desired, be fitted over the top of the column to prevent disturb-
ance of the surface.
Meanwhile dissolve not more than 0-5 g. of a mixture of
crude o- and />-nitroaniline in 30 ml. of dry benzene and then
allow this solution to enter the tube slowly through the dropping-
funnel. Immediately this solution has all entered the tube,
continue running in the pure solvent, and develop the chromato-
gram by collecting the benzene from the bottom of the tube and
running it again through the top of the tube. Continue in this
50 PRACTICAL ORGANIC CHEMISTRY
way until the two yellow bands have become distinct and
separate during their passage to the lower portion of the column.
Then continue the washing with fresh benzene until each band
has been separately eluted in about 150 ml. of benzene, that of the
o-nitroaniline emerging first from the tube.*
Concentrate each of the two solutions (or eluates) to about
20 ml. by distilling off the greater part of the benzene, the dis-
tilling-flask being immersed in the boiling water-bath. Then
pour the concentrated solution into an evaporating-basin, and
evaporate the remaining benzene (preferably in a fume-cup-
board) in the absence of free flames, i.e., on an electrically heated
water-bath, or on a steam-bath directly connected to a steam-
pipe. Wash the dry residue from the first eluate with petrol and
then dry it in a desiccator: pure o-nitroaniline, m.p. 72°, is
obtained. Wash the second residue similarly with a small quan-
tity of benzene and dry: pure p-nitroaniline, m.p. 148°, is
obtained. Record the yield and m.p. of each component.
NOTE. For more delicate work, highly purified solvents are necessary, but
for the above experiment dry technical benzene is suitable.
PAPER CHROMATOGRAPHY
Filter paper is made of highly purified cellulose which, being a polyhydroxy-
compound of high molecular weight, both absorbs and retains water molecules
strongly. Consequently if a small quantity of mixed solvent (one component of
which is water and another being almost insoluble in water) is placed in a tall
cylinder and a strip of the filter paper then suspended vertically in the vapour
above the solvent in the closed cylinder, the paper will absorb preferentially the
water molecules. The film of the solvent molecules on the paper will therefore
contain all the solvent constituents, but with a greater proportion of water
molecules than that in the original mixed solvent.
A drop of an aqueous solution of the mixture to be separated is now placed
near the bottom of the paper strip and allowed to evaporate in the air. The
strip is now again suspended in the closed cylinder, but with the bottom of
the strip just immersed in the solvent. The capillary action of the paper will
cause the solvent to rise steadily up the strip, and during this process the
solvent, which now contains the mixture in solution, is continuously extracted
by the retained water molecules in the paper. A highly hydrophobia (water-
repellent) solute will move up closely behind the solvent-front, whereas a
highly hydrophilic solute will barely leave the original point where the drop
of the mixed solutes in solution has been dried. In an intermediate case,
* The chromatographic separation should whenever possible be completed in
one operation. If, however, shortage of time necessitates an interruption, this
can most conveniently be made immediately after the first band has been
completely eluted, whereupon the lower end of the tube is closed by a short
piece of rubber tubing carrying a screw-clip. Great care should be taken how-
ever not to allow even the top of the column to run dry.
METHODS AND MANIPULATION 51
however, the extent to which a particular solute has moved, relative to the extent
to which the solvent has moved, known as the R F of the solute, will be a function
of the partition coefficient of the solute between the solvent and the film of
retained water.
When the ascending solvent-front has reached a convenient height, the strip
is removed, the position of the solvent-front marked, and the paper strip dried.
The positions of the various solutes, if they are coloured compounds, now
appear as clear separate spots. Frequently however, the solutes are colourless,
and the position of their spots must be determined by indirect methods, such
as their fluorescence in ultraviolet light, or their absorption in such light (when
the spots appear almost black), or by spraying the paper with a dilute solution
of a reagent which will give a coloured insoluble derivative with the solutes.
The first of the two experiments given below illustrates the separation of
amino-acids, now an almost classic example of the use of paper chromatography:
the second illustrates the separation of anthranilic acid and 7V-methylanthranilic
acid. Both experiments show the micro scale of the separation, and also the
fact that a mixture of compounds which are chemically closely similar can be
readily separated, and also can be identified by the use of controls.
The second experiment requires far less time than the first (cf. p. 54).
Separation of Glycine (I), ( ±) Proline (H), and
( ± ) Phenylalanine (IH)
These three amino-acids are colourless and readily soluble in water:
NH 8 -CH 2 -COOH H2C CH 2
(I) I I
H8C CH-COOH
C 6 H 6 -CH 2 -CH-COOH \ /
NH 2 N
(HI) (II) H
like most a-amino-acids, they give marked colours with "ninhydrin''
(IV) (systematically 2,2-dihydroxy-i,3-dioxohydrindene), and these
colours are used to detect the final position of each acid on the paper
strip.
Apparatus. A strong glass cylinder E (Fig. 25(A)), which is con-
veniently about 45 cm. high and about 6 cm. internal diameter, is
fitted with a rubber bung F having a glass rod G which passes through
the centre of the bung, and which is bent at the lower end as shown.
The paper strip can be folded over the horizontal arm of G, and held
in position by two plastic clips H:alternatively it can beheld by two
metal paper-clips, but in this case two glass microscope slides should
be placed across the strip and under the clips, to protect the paper
from the metal.
A i-litre measuring-cylinder may be used in place of the cylinder E,
but when the bung F is in position, any gap at the Hp of the cylinder
must be tightly plugged with cotton-wool.
The paper strips (conveniently 40 X 4 cm.) should be cut from
PRACTICAL ORGANIC CHEMISTRY
Whatman No. i filter-paper, and handled as little and as cleanly as
possible.
Spray. For most purposes a simple spray device, based on the ordinary
scent-spray, suffices. A finer and less intermittent spray can be obtained using
the apparatus shown in Fig. 26. A narrow glass cylinder J has a ground-glass

A'B'

(A)
FIG. 25.
neck into which the attachment K fits securely. This attachment consists
essentially of the central neck K, which has two short inlet tubes, L being
horizontal and M bent upwards as shown, and a long curved outlet tube N
which is tapered to a small orifice at the end. The lower part of K within the
cylinder J consists of a tapering tube P having a small hole Q at one side: the
open base of P is curved inwards as shown to form a fiile capillary-tube which
reaches to the upper end of the outlet tube N. (Alternatively, the capillary tube
can be drawn out from a short length of tubing which fits inside P, and is held
in position by being lightly fused to the inside lower rim of P at two opposite
points.) The spraying solution is put into J, and the inlet tube L connected to
a high-pressure air supply. "When J is grasped in the hand, and the tube M
closed with the forefinger, a very fine spray is blown from N, and its duration
can be immediately controlled by thus opening or closing M.
Reagents. (A) Amino-acid solution. A solution of 5 mg. of glycine,
5 mg. of proline, and 5 mg. of phenylalanine in i ml. of water.
(B) Control solution. A solution of 5 mg. of glycine in i ml. of water.
(C) Mixed solvent. A well-shaken mixture of 20 ml. of redistilled
H-butanol, 9-5 ml. of water, and 5-5 ml. of 95% ethanoL
(D) Spraying solution. A solution of 0-2 g. of ninhydrin in a mixture
of 99 ml. of redistilled n-butanol and i ml. of glacial acetic acid.
Method. Draw a light pencil line across the paper strip about 3 cm.
from the bottom (Fig. 25 (B) ), and mark two points A' and B' 2 cm.
METHODS AND MANIPULATION „
apart symmetrically on the line as shown. By means of a fine glass
pipette, drop sufficient of solution (A) on the point A' to form a circular
zone about 0-5 cm. in diameter. Wash pipette thoroughly, and then
similarly place solution (B) on the point B'. Dry the strip in the air.
Now place 35 ml. of the mixed solvent (C) in the clean cylinder E,
and suspend the strip, as described above, to the horizontal arm of G
(Fig. 25(A)); adjust the position of the strip so that, when the bung
is firmly in position, the bottom of the paper-strip is about 5 mm.
above the solvent. Place the cylinder for 5-8 hours in a draught-free
place, such as a cupboard, where the temperature is reasonably constant.
Now lower the paper-strip, which has become saturated with the
solvent vapour molecules, so that it dips about 5 mm. into the solvent.
Then close the cylinder, and set it aside as before for 12-18 hours, by
which time the solvent will have risen about three-quarters of the
height of the strip.
Then remove the strip and dry it in a stream of cold air, either from
a blower, or by pinning it to the lower edge of a fume-cupboard window
having a vigorous draught already in operation. Then spray the strip
lightly but uniformly with the ninhydrin solution (D) in a fume-
cupboard, and dry as before.
The positions of the three amino-acids are shown clearly by the
colour of their zones or spots, the proline being yellow and the glycine
and phenylalanine being blue. Note the R p value for each amino-acid:
Distance moved by centre of solute zone
p
Distance moved by solvent front.
The control solution (B) is used in this experiment to differentiate
between the blue spots of glycine and phenylalanine. It will be seen
that the R F value of phenylalanine is greater than that of glycine.
The position of the spots should be marked in pencil, for the colours
fade after some time.
NOTE. The period of 5-8 hours recommended above for attaining
an equilibrium between the vapour molecules of the mixed solvent
and those absorbed by the paper strip is essential if accurate RF values
are required for identification of mixed amino-acids. To illustrate the
separation, as in the above experiment, this period may be reduced to
about 2 hours.
Separation of Anthranilic acid and N-Methylanthranilic acid.
Both these acids are colourless, but the "spots" of each acid on a filter-paper
strip show up in ultraviolet light as intense blue fluorescent zones. They can
also be detected, but considerably less sensitively, by spraying with ethanolic
ferric chloride solution, which gives with N-methylanthranilic acid a purple-
brown coloration.
N-Methylanthranilic acid is very readily prepared (p. 222). Prepare a
sample of this acid and recrystallise it 2 or 3 times from ethanol until it has
m.p. 177° and is "pure".
54 PRACTICAL ORGANIC CHEMISTRY
This experiment requires less time than the former, for the paper strip comes
into equilibrium with the solvent vapour much more rapidly, and can then be
inserted into the solvent without intermediate drying.
Reagents. (A) Anthranilic acid. A solution of 20 mg. of the pure
acid in 20 ml. of methanol.
(B) N-Methylanthranilic acid. A solution of 10 mg. of the acid
(recrystallised as above) in 20 mg. of methanol.
(C) Mixed acids. A solution containing 10 mg. of each acid in
20 ml. of methanol.
(D) Mixed solvent. Add 10 ml. of concentrated aqueous ammonia
(d, o-88o) to 40 ml. of redistilled n-butanol and thoroughly mix to
obtain a complete solution.
Method. Prepare a paper strip from Whatman No: i filter paper,
as in the previous experiment, and draw a light pencil line about 3 cm.
from the bottom (cf. Fig. 25(6)). Mark three points A', B' and C' sym-
metrically on this line, if possible 2 cm. apart. Using the fine pipette,
or a capillary tube, apply sufficient of solution (A) to the point A' to
give a damp spot about 0-5 cm. in diameter. Using a thoroughly
washed pipette or a fresh capillary tube on each occasion, apply solution
(B) and (C) to the points B' and C' respectively. Dry the strip in
the air.
Place 40 ml. of the mixed solvent (D) in the chromatogram cylinder,
and suspend the dried strip in the closed cylinder (cf. p. 223) for at
least 30 minutes to allow the paper to come into complete equilibrium
with the mixed solvent. Then gently lower the strip until the bottom
edge dips about 5 mm. into the solvent. Allow the chromatogram to
develop overnight protected from draughts.
Next day, hang the paper from the edge of the fume-cupboard
window in the full draught of the fan to dry, and immediately mark
the position of the solvent front.
Inspect the paper in ultraviolet light—conveniently in front on a
Hanovia ultraviolet strip light—in a dark room. The acids show up
as intense blue fluorescent spots. Mark with a pencil the positions of
all spots. The position of the two spots arising from solution (C)
should be compared with the single spots arising from solutions (A)
and (B). It is probable that the solution (B) of "pure" N-methylan-
thranilic acid may also reveal a faint spot corresponding to anthranilic
acid still present in minute traces in the methylated acid (cf. p. 223).
Record the Rp values of the two acids: under the above conditions
the anthranilic and the N-methylanthranilic acid should have RP
values of 0-28 and 0-55 respectively.
Finally spray the paper with neutral i% ethanolic ferric chloride
solution: the methylanthranilic acid spot develops a purple-brown
coloration, whereas the anthranilic acid gives only a very faint pink
coloration.
If an alternative mixed solvent is required, shake thoroughly a
mixture of 20 ml. of distilled water and 40 ml. of the w-butanol, then
METHODS AND MANIPULATION 55
allow the mixture to separate, and use the upper (organic) layer. Under
the above conditions, but using this solvent, the spots are decisively
but not so widely separated, for the RF values for the anthranilic and
the methylanthranilic acid are now 0-68 and 0-81 respectively.
ION EXCHANGE
The principle of ion exchange is employed in the separation of organic com-
pounds on a semi-micro scale or micro scale. Broadly speaking, the use of ion
exchange materials* is, in some respect, similar to the use of adsorbents in
ordinary chromatography. Ion exchange materials are usually described as
(a) cation exchange resins and (6) anion exchange resins.
Ion exchange materials are usually resins with acidic or basic groups incor-
porated into their molecular structures. Such resins are commercially available
and are usually made by the co-polymerisation of styrene and divinylbenzene.
The latter forms cross linkages between chains of polymerised styrene to give
a lattice structure. Suitable groups upon which the exchange principle depend
can be introduced either before or after condensation. For example a "sulphon-
ated exchanger" can be prepared from suitably sulphonated monomers or by
sulphonating the final resin under controlled conditions. Fig. 27 represents
the essential features of such a sulphonate exchanger.
—CH-CH 2 —

,'SO3H

CH-CH2 CH-CH2—CH—CH2 CH

-SO3H
SO33H I SO3H
CH2—CH—CH2-
FIG. 27.
Cation exchange resins usually contain as their active principle these sulphonic
acid groups although they may contain carboxylic acid groups instead. Those
polymers containing —SO3H groups are known as strong acid cation resins,
whereas those containing —COOH groups are designated weak acid cation
resins. Both these cation exchange resins may be looked upon as insoluble acids
of extremely high molecular weight. Anion exchange resins usually contain as
the active exchange principle quaternary ammonium groups (Fig. 28) and may
* The student who is interested in details of the physical principles involved
and of further applications of ion exchange should consult Ion Exchanges in
Organic and Biochemistry by Calvin Calmon and T. R. E. Kressman. (Inter-
science Publication Inc., New York.)
56 PRACTICAL ORGANIC CHEMISTRY
be regarded as very strong insoluble bases (or salts of such bases) of extremely
high molecular weight. Such polymers are designated as strong base anion
resins. There is also a class of weak base anion resins which contain amino groups
in place of the quaternary ammonium groups.
-CH H-

CH2-N(CHj)3Cl CH 2 N(CHj) 3 Cl
CH CH2 CH-

CH2N(CHj)3Cl
FIG. 28.

Ion exchange resins are, in general, not suitable for macro-work owing to the
limited number of "exchange" groups. Among the more important appli-
cations of ion exchangers are:
(1) Conversion of a sodium salt of a carboxylic acid into the free acid: e.g., if
R-SO,H represents the cation exchange resin:
R-SO3H-KCH8COONa -»• R-SO3Na-HCH8COOH
(2) Removal of bases from mixtures of bases and neutral compounds such
as alcohols.
(3) Conversion of the salt of a weak base into the free base: e.g., if
+
[R'N(CH3)8OH] represents the cation exchange resin:

+ _ +_ + - -i- —
[R-N(CHa) 8 OH] + C 6 H 5 NH 3 Cl-^ [R-N(CHJ1Cl] + C6H5NH8OH
I
C6H5NH1 + H1O

(4) Removal of acids from mixtures of acids and neutral compounds.

Conversion of sodium citrate into citric acid.


This conversion cannot easily be carried out on a semi-micro scale by ordinary
chemical means. Liberation of an acid from one of its salts by dil. H1SO4 is
feasible when the organic acid is insoluble in water (e.g. an aromatic acid) or
METHODS AND MANIPULATION 57
when it is volatile (e.g. acetic acid). Citric acid is water-soluble and non-
volatile and therefore cation exchange is a particularly suitable method of
liberating it from its salts.
Method. Prepare a slurry of a strong acid cation resin (such as
Amberlite I.R-i2o(HO)*) in distilled water. Place a thin plug of glass
wool at the base of a 50 ml. burette. Now pour the slurry into the
burette until the latter is about half full. Open the tap of the burette and
pour distilled water through the slurry until all the air bubbles have
been removed. Drain off most of the water, but do not allow the resin
to become uncovered at any time during this or subsequent operations.
Now pass ioo ml. of io% hydrochloric acid solution through the resin
and then wash it thoroughly by passing distilled water down the column
until the washings leaving the burette are neutral to methyl orange.
Close the tap of the burette. This column is now ready for use. Prepare
a solution of 0-05 g. of sodium citrate in ioo ml. of water. Now pass this
solution down the column at the rate of 5 ml. per minute by opening the
tap of the burette to a suitable extent. Collect the runnings. When all
the mixture has been added, wash the column with 50 ml. of distilled
water, and add these runnings to those previously collected. Evaporate
the combined runnings or "effluent" in order to obtain pure citric
acid, m.p. iooc.
The column of resin must now be "regenerated," i.e. the retained
ions must be removed by passing an excess of "regenerant" (in this
case io% HCl) down the column as described above. The column 13
then washed with water and is ready for a new cycle of operations.
Note that the column must not be allowed to become dry.
As a corollary to the above it should be pointed out that the exchange
is in some instances stoichiometric and therefore the amount of cation
in solution can be estimated by passage through a hydrogen exchanger
as above and subsequent titration of the acid in the effluent.
(2) Removal of bases from mixtures of bases and neutral compounds.
The procedure here is essentially the same as in (i) above. The base
is retained by the column. Use a solution of 0-05 g. of benzylamine
and o-i g. of mannitol in ioo ml. of water. The effluent contains only
mannitol.
(3) Conversion of the salt of a weak base into the free base. Prepare
a column of a strong base anion resin (such as Amberlite IRA-4oo(OH)*)
washed with distilled water as above. Drain off most of the water and
then allow ioo ml. of 71//2.Na2CO3 solution to pass through the column
at 5 ml. per minute. Again wash the column with 200 ml. of distilled
water. Dissolve 0-05 g. of aniline hydro chloride in ioo ml. of distilled
water and pass the solution down the column. The effluent contains
aniline in solution and free from all other ions.
(4) Removal of acids from mixtures of acids and neutral substances.
Prepare a column of a strong base anion resin and treat it with sodium
* Obtainable from British Drug Houses, Ltd., (Laboratory Chemicals Divi-
sion), Poole, Dorset, BH12 4XN.
58 PRACTICAL ORGANIC CHEMISTRY
carbonate as in (3). Prepare a solution of 0-025 g. of citric acid and
0-25 g. of glucose in ioo ml. of distilled water. Pass this solution down
the column at the rate of 5 ml. per minute. Collect the effluent and
wash the column with ioo ml. of distilled water. Add this to the main
effluent and distil off the water until a small volume is obtained, then
evaporate to obtain pure glucose. [The citric acid is retained on the
column and can if desired by recovered in solution by eluting the
column with ioo ml. of M1'2 ammonium carbonate solution.]
Regenerate the column by washing with water, TlI 2.Na 2 CO 3 solution,
and again with water.
Thin Layer Chromatography
This is used extensively for qualitative analysis, for it is a rapid process and
requires simple apparatus. The adsorbent is usually a layer, about 0-25 mm.
thick, of silica gel or alumina, with an inactive binder, e.g. calcium sulphate, to
increase the strength of the layer. A 1:1 slurry of the absorbent and methanol is
commonly coated on glass plates (5 X 20 cm. or 20 X 20 cm.), but microscope
slides are convenient for routine work. Various spreading devices are available
for the larger plates, or they may be bought ready-prepared. Microscope slides
may be prepared by dipping them in pairs back-to-back in the slurry and quickly
withdrawing them. The long edges are wiped clean with thumb and forefinger,
and the plates separated and placed face-upwards on racks, and the absorbent
activated by drying at no for 30 minutes; the plates can then be stored in a
desiccator.
The mixture to be separated is dissolved in a suitable solvent and spotted on to
a pencilled line at the bottom of the t.l.c. plate, ca. i -o-i -5 cm. from the end. A
suitable dropping tube may be made by drawing out the middle of a m.p. tube
with a micro-burner and breaking the tube in the middle. The dropper is filled
by capillary action and is discharged when the liquid at the tip drops on to the
untouched absorbent surface; the spot should be 2-5 mm. in diameter.
When the solvent around the spot has evaporated, the plate is placed vertically
in a glass developing 'tank' (a cylinder for small slides) which contains a small
quantity of the solvent and is lined with filter-paper dipping into the solvent;
the level of the latter is adjusted, preferably with a pipette, so that the lower
edge of the absorbent layer is under the solvent but the spot is above this level,
and the top of the cylinder is then firmly closed. The solvent rises through the
adsorbent layer, and the components of the mixture ascend at different rates
depending on their affinities for the adsorbent.
When the solvent has nearly reached the top of the adsorbent layer, the
components should be well separated. The relative distance travelled by the
components can be increased by using a solvent of higher or lower polarity in
the order of increasing eluting power:
petroleum < benzene < chloroform < ether < ethanol
The plate is removed from the tank, the position of the solvent front marked,
and the solvent allowed to evaporate from the plate. If the components of the
mixture are coloured, the separation is obvious; if colourless, they must be
located either by viewing under U.V. or by standing the plate in a closed dry
'tank' containing crystals of iodine, whose vapour makes brown spots show up.
The Rp values of the components are determined as before (p. 53).
Methods and Manipulation on a Semi-micro Scale.
INTRODUCTION. When only very small quantities of organic materials
are available their manipulation must necessarily be carried out on a
correspondingly small scale. This occurs frequently in research prob-
lems, but small-scale preparative work is often of value to the student
because considerable economy of materials and of time can be achieved.
It is emphasised, however, that the proper training for the organic
chemist must rest upon the correct understanding and thorough
practice of the manipulations on the macro-scale already described, and
that he should consider small-scale work as a sequel to and not as a
replacement of the above standard techniques.
Preparative work is sometimes divided into three categories. This
division is entirely arbitrary and the categories overlap, but they may
conveniently be classified thus:
Scale Remarks
(a) Macro. Usually i g. to 200 g. for solids and 5 g. to 200 g.
for liquids.
(b) Semi-micro. 50 mg. to i g. for solids and i g. to 5 g. for liquids.
(c) Micro. Below the above limits.
The difficulties of working with small quantities of liquids are much
greater than with small quantities of solids. For example a competent
worker can, and does in fact, often work with i oo mg. of solid without
any special apparatus. With liquids this is often not practicable because
of the much greater losses entailed, particularly when it is realised that
one ordinary-sized drop weighs about 50-100 mg. The account
which follows gives details of modifications of standard apparatus
suitable for the semi-micro scale defined above.
General Considerations. With liquids and solutions the most
serious losses are due to (a) transference from spherical flasks and
difficulties of drainage, (b) retention by filter-papers, (c) absorption by
large corks. As containers for small quantities of liquids it is therefore
often convenient to use pear-shaped flasks A and conical test-tubes or
centrifuge-tubes B (Fig. 29). (In this and subsequent figures, approxi-
mate dimensions are given to indicate a convenient size.)
The transference of a liquid from one vessel to another is best carried
out by means of a dropping pipette A (Fig. 30). For measuring out a
definite volume of liquid it is obviously an advantage to have a cali-
brated pipette B (Fig. 30) of i or 5 ml. total capacity. Alternatively,
semi-micro burettes reading to 0-02 ml. are particularly convenient for
class work.
For the separation of immiscible liquids a small separating funnel
of the conventional type should be used whenever practicable, a pear-
shaped funnel (Fig. 16, p. 35) of 5-10 ml. capacity being particularly
59
6o PRACTICAL ORGANIC CHEMISTRY
convenient. For separations on a smaller scale a dropping-pipette
should be used: for the removal of an upper layer, the bent pipette
(Fig. 31) is recommended. An ordinary hand centrifuge may be
employed to promote a clean line of demarcation between two im-
miscible liquids which show a tendency to emulsify.

7-5 cm.
7-5 cm.

V
FIG. 29. FIG. 30. FIG. 31.

In order to minimise the absorption of liquids by corks, single pieces


of apparatus are used wherever possible.
A skilled worker can use a micro-Bunsen burner for most types of
heating. Nevertheless, as there is a tendency for a liquid to shoot out
of a small test-tube when heated, it is preferable to place the tube in a
hot water-bath or in a metal heating block. A small glycerol bath is
suitable for distillations and heating under reflux, the glycerol being
subsequently easily removed from flasks, etc., by washing with water.
Determination of Boiling-points. The following alternative
methods are recommended, (a) Draw one drop of the liquid into a
capillary tube so that the drop is about i cm. from one end.
Hold the tube horizontally and quickly seal this end in a micro-
burner. Attach the tube (with the open end upwards) to a
thermometer in the melting-point apparatus (Fig. i(c), p. 3) so
that the trapped bubble of air in the capillary tube is below the
surface of the bath-liquid. Now heat the bath, and take as the
b.p. of the liquid that temperature at which the upper level
of the bubble reaches the level of the surface of the bath liquid,
(b) Prepare a fairly wide capillary tube A (ca. 4 mm. X 8 cm.)
(Fig. 32). Using a fine pipette insert about i cm. length of the
liquid into the bottom of the tube. Now place in the tube A a
fine inverted melting-point tube B of about i mm. diameter,
sealed at the upper end. Fasten the capillary tube to the ther- FIG. 32.
mometer by means of a rubber band and place in a melting-point
apparatus. Heat slowly until a stream of bubbles rises from the bottom
METHODS AND MANIPULATION 61
of the capillary tube, then remove the source of heat and, as the bath
cools, take as the b.p. that temperature at which the liquid recedes into
the inverted tube B.
Determination of Melting-points. The determination of the
melting-point, as described on pp. 2-4, is of course in itself a micro-
method. Even so, when working on a very small scale it is advantageous
to use either:
(a) Electrically heated melting-point apparatus (Fig. 33), or
(b) Microscope hot stage apparatus (Fig. 34).
(a) Electrically heated melting-point apparatus.
With this type of apparatus (Fig. 33) high temperatures can be reached
with safety and the dangers of hot oil or concentrated sulphuric acid
are avoided.
Electric Light A metal cylinder A contains
Bulb m.p. Tube
two small holes. Into one of
these the thermometer, is
placed and into the other
(arranged centrally) is placed
Thermometer the melting-point tube. The
cylinder is pierced by a hori-
zontal tunnel so the melting-
point tube can be observed
FIG. 33- during heating. A lens is
fixed in front of the horizontal tunnel so that minute changes can be
observed on very small amounts of material in the melting-point tube.
The cylinder is heated electrically by an insulated resistance, controlled
by a rheostat. The melting-point tube is illuminated electrically from
behind. After a determination, the metal cylinder and surrounding
element can be cooled very quickly by a jet of cold air (from bellows
or from compressed air mains).
(b) Determination of Melting-point on Microscope Hot Stage
The advantages of this method are twofold (i) It is possible to
observe minute changes in colour and structure before and during the
process of melting. (2) It is possible to use a single crystal which, e.g.,
is often obtained from a semi-micro sublimation.
The instrument (Fig. 34) is fixed by screws on to the stage of the
microscope. An electrically heated stage S supports a removable
rim R, and a glass slide G. The heating apparatus is connected to a
rheostat. A thermometer T is inserted into a long cylindrical hole
passing below the centre of the stage. Light from the mirror of the
microscope passes through the optical condenser below the hot stage and
then through a small opening in the latter so as to illuminate the sample.
If the apparatus has not been used for some time, ij should be heated
to about 140° to drive off any moisture. After cooling, a few crystals
of the substance are placed on the glass slide G. A small cover glass,
62 PRACTICAL ORGANIC CHEMISTRY
C, is then placed firmly on the slide. The latter is then inserted into
the stage in such a position that the sample is directly above the light
opening. A glass baffle, B, is placed over the sample, so as to protect
the microscope lens from too much heat. A large glass cover is then
placed completely over the rim B. The sample is now brought into sharp
focus and the temperature raised by adjustment of the rheostat. As
usual when taking melting-points, the temperature should be almost
stationary at the actual melting-point.

FIG. 34.
Heating under Reflux. For this purpose, a glass water-condenser
of length ca. 25 cm. can be used. When boiling very small volumes of
liquid under reflux, the "cold finger" A (Fig. 35) is of great value. The
cold finger, if provided with a shoulder, can rest on the rim of a test-
tube or flask, or it may be inserted through a cork having the usual
groove cut in the side to allow escape of gas (cf. Fig. 37).
The heating of the vessels is accomplished by means of
a small bath or a micro-Bunsen burner. The vessel can
be clamped at such a distance from the burner that the
contained liquid boils gently under reflux. Smooth boil-
ing is ensured by the addition of 1-2 minute pieces of
unglazed porcelain, or of a short piece of melting-point iocm.
tubing open at both ends.
Stirring. In semi-micro work stirring is not often
necessary as manual agitation usually suffices. When pro-
longed stirring is required, a small glass stirrer attached
to a motor is recommended for reactions taking place in
open flasks. For closed systems a small spring disc is
available* which fits snugly into the neck of the flask.
The disc contains a hole, centrally placed, through which FIG. 35-
a small glass stirrer can be pushed. The stirrer should be
smeared with a very small amount of silicone grease where it passes
through the spring disc. A relatively powerful motor is required for
this apparatus.
A magnetic stirrer is also recommended for semi-micro work.
A small bar of glass-covered steelf is placed in the liquid contained
* Supplied by Messrs. Geo. Angus Ltd., Coast Road, Wallsend, Northum-
berland.
t Alternatively, the steel bar may be encased in Tevlon plastic, which pre-
ferably has a small ridge of the plastic around its middle to prevent it lying flat
in the flask.
METHODS AND MANIPULATION
in a small flat-bottomed flask which is placed over a motor containing
a horizontally-rotating magnet.
Distillation. This process is carried out in the apparatus shown in
Figs. 36, 37 and 38. The distillation apparatus (Fig. 36) is of very
general application and is made in one piece.
Distillations on the semi-micro scale "can
also be carried out in the simple pear-shaped
distilling flask A (Fig. 37). The distillate is
collected in the 'centrifuge-tube' B placed in
the bottom of the vessel C. The latter is a
boiling tube with a side-arm fused on at 45°.
IO cm.
This arm is connected to that of the flask by
a cork. A "cold finger" D serves to condense
the vapour issuing from the side-arm of the
flask. Distillation in this apparatus must be
performed very slowly to ensure efficient
FIG. 36.
condensation and collection of the distillate
in B. This type of apparatus is particularly suitable for liquids of high
boiling-point and especially for substances that solidify on cooling.
As the side-arm of A is not cooled, condensation is not usually likely
to take place before the distillate reaches B. As this apparatus is
virtually closed except for the groove in the cork of C, it is also con-
venient for the distillation of pungent and lachrymatory materials (e.g.,
benzyl chloride).

Groove

IO cm.

FIG. 37. FIG. 38.


All thermometers for semi-micro preparations must have very small
bulbs. They may often be inserted into flasks through a short "collar"
of rubber tubing in place of the customary corks.
Distillation Technique. With all distillations on a semi-micro
scale it is essential to heat the liquid so slowly that a "cushion" of its
64 PRACTICAL ORGANIC CHEMISTRY
vapour envelopes the bulb of the thermometer for a sufficiently long
time to enable the thermometer to register the correct temperature.
It is for this reason that the side-arm of the flask proceeds upwards
before passing downwards. By this device a "cushion" of vapour can
be maintained round the bulb of the thermometer before the required
fraction is distilled.
Reflux Distillation Unit, The apparatus shown in Fig. 38 is a
specially designed distillation-unit that can be used for boiling liquids
under reflux, followed by distillation. The unit consists of a vertical
water-condenser A, the top of which is fused to the side-arm condenser
B. The flask C is attached by a cork to A. This apparatus is particularly
suitable for the hydrolysis of esters (p. 99) and anilides (p. 109), on a small
scale. For example an ester is heated under reflux with sodium
hydroxide solution while water is passed through the vertical condenser;
water is then run out of the vertical condenser and passed through the
inclined condenser. The rate of heating is increased and any volatile
product will then distil over.
Fractional Distillation. Fractional distillation on a semi-micro
scale can be carried out satisfactorily with the fractionating column
shown in Fig. 39. The column is 10 cm. long and is filled with pieces

to Pump

IOcm.

FIG. 39. FIG. 40.

(3-4 mm. long) of very narrow glass tubing. As in all fractionations


the distillation must be carried out very slowly and in this connection,
particular use is made of the ''upward" bend of the side-arm so as to
record the maximum temperature of the issuing vapour.
The apparatus shown in Fig. 38 can also be used for fractionation
by placing a secure plug of glass wool at the base of the vertical con-
denser and then filling it with short pieces of glass tubing.
METHODS AND MANIPULATION 65
Distillation under reduced pressure. The student should first
read details of this operation on a macro-scale (p. 28). For micro-scale
work the apparatus shown in Fig. 40 is very convenient. A small pear-

FIG. 41(D).

shaped flask of 5 ml. capacity is fitted with a small side-tube through


which a piece of glass tubing can be passed. The latter is held in
position by a rubber bung,* and is drawn out into a fine capillary tube
to act as an air-leak. The upper end of the
tubing is fitted with pressure tubing and a
screw-clip to regulate the flow of air. Distil-
ling flasks of alternative design are shown in
Figs. 4i(A) and 41(6).
With a single receiver tube as shown in
Fig. 40 it is necessary to interrupt the distil-
lation each time the receiver is changed. For
more precise work a multiple receiver as
shown in Fig. 42 should be used. The lower
part L of this apparatus contains 6 small
collecting tubes C, eachf supported in a wire
hoop attached to a fixed vertical glass rod.
The receptacle L is attached to the upper part
of the apparatus by a ground-in glass joint, J,
carefully lubricated by silicone grease. By
gently rotating the receptacle L about the
ground-glass joint J, it is possible to collect
the different fractions in the separate tubes
without stopping the distillation, and hence
without alteration of pressure.
* The type of apparatus shown in Fig. 40 can be
obtained with ground-in glass joints thus obviating
FIG. 42. the use of rubber bungs.
f Each tube C should have an identification mark, so that the b.p./pressure
of the contents of each can be recorded during the distillation.
66 PRACTICAL ORGANIC CHEMISTRY
Steam Distillation. A compact and efficient apparatus is shown
in Fig. 43. The liquid to be steam-distilled is placed in the tube A
and water is placed in the outer flask B. On heating B, steam passes
into the inner tube A through the inlet tube C, and steam-volatile
compounds are rapidly distilled and collected in the receiver placed at
the end of the condenser D.
For small quantities of compounds which are readily volatile in
steam, it will often suffice to add water to the crude material in the
reaction flask (e.g., Fig. 36) and to heat directly with a small flame.

12 cm.

FIG. 43- FIG. 44-


A very suitable apparatus for semi-micro steam-distillation, particu-
larly for suspensions that are likely to "bump" badly, is shown in
Fig. 44. This consists of a 50 ml. Kjeldahi flask, clamped at an angle
of 45°, and fitted with a long glass tube for the inlet of steam. The
outlet-tube is bent twice, first at 135° and then at 45° as shown, and
fitted into a small water-condenser.
Steam generator. For small scale work the steam generator
^D, Fig. 15, p. 33) is too cumbersome for the production of a small
amount of steam. It is preferable to use a 250 ml. conical flask fitted with
cork containing a vertical safety tube and an outlet-tube (Fig. 44).
Care should be taken that the length of rubber tubing connecting the
steam outlet tube to the flask containing the material to be distilled
should be as short as possible and should not contain kinks.
Crystallisation and Filtration. Crystallisation is carried out in
apparatus of conventional type but reduced in size. Glass rods should
METHODS AND MANIPULATION 67
be about 10 cm. long and 2 mm. in diameter. It is advisable to use
solvents in which the solute is sparingly soluble, so that larger volumes
of liquid can be employed. Light petroleum and cyclohexane are
often satisfactory for this purpose.
Choice of Solvent. In general, a higher boiling solvent is preferable
to a low-boiling solvent, as evaporation is then considerably less.
When the correct solvent for recrystallisation is not known a pro-
cedure similar to that given on pp. 15-16 should be followed, but on the
semi-micro scale not more than io mg. of the solid should be placed
in the tapered-end test-tube (Fig. 29(5)) and about o-i ml. of the solvent
should be added from the calibrated dropping-pipette (Fig. 30(8)).
If the compound dissolves readily in the cold, the solvent is unsuitable,
but the solution should not be discarded. [In this case recourse
should be had to the use of mixed solvents (p. 18). For example if the
substance is very soluble in ethanol, water should be added from a
calibrated pipette with shaking to determine whether crystallisation will
now take place, indicated by a ''cloudiness" or by the separation of solid.]
If the solid does not dissolve in the cold solvent gently heat the
mixture over a micro-Bunsen burner or in a small water-bath until the
liquid boils. Continue to add o-i ml. portions of solvent until the
solid dissolves. [If more than about i ml. of solvent is required, the
solvent is considered unsatisfactory.] If a clear solution is obtained, CDO!
the tube and scratch it below the surface of the solution with a very fine
glass rod and proceed as suggested on p. 16. In general, the products
from the ''choice of solvent" investigation are not discarded but added
to the main bulk of the crude product for recrystallisation.
The filtration of crystals is carried out using a small conical Buchner
funnel (C, Fig. 4, p. io) or a funnel of similar design but having a
sintered filtration plate. Alternatively an ordinary conical funnel in
which is placed a circular perforated plate can be used.
The complete filtration apparatus is shown in Fig. 5, p. u. A simpler
and cheaper apparatus is shown in Fig. 45. This consists of a boiling-
tube A having a side-arm for connection to the pump: the tube A is
conveniently held in a wooden or cork block B or in a clamp. The
funnel F may be fitted into A through a pliable rubber disc D: the
latter is more useful than a cork since it covers tubes of various dia-
meters. The filtrate is collected in the centrifuge-tube T.
For the filtration of very small quantities of crystals, the simple
apparatus shown in Fig. 46 is often used. It consists of a fine glass rod
(sometimes termed a "filtration nail") which is flattened at one end,
the flattened surface being preferably roughened. It fits as shown into
a small funnel which replaces F (Fig. 45). A circular piece of filter-paper
is cut (e.g., with a clean sharp cork-borer) so as to fit completely and
snugly over the flat end. After draining, the "nail" is raised and the
filter-paper and crystals are removed with forceps and dried.
The filtration of hot or boiling liquids requires care, as rapid evapora-
tion is likely to occur. Evaporation is minimised by the use of a
68 PRACTICAL ORGANIC CHEMISTRY
cylindrical tube T (Fig. 47) furnished with a filter-plate or sinter.
The tube T can be fitted into an adaptor B (Fig. 47), or it may be
inserted directly through the disc D (Fig. 45) so that the filtrate collects
in a suitable tube placed in the receiver A (Fig. 45). Adaptors such as
B (Fig. 47) are of considerable use in many kinds of micro-chemical work.

Mem.

12 cm.

FIG. 45. FIG. 46. FIG. 47.

Drying of crystals. Whenever possible crystals should be dried


in a small vacuum desiccator containing a suitable desiccant. The
latter depends upon the nature of the solvent used (cf. p. 19). However
for most purposes anhydrous calcium chloride is satisfactory. If a
hydrocarbon has been used in the recrystallisation, a few thin fresh
shavings of paraffin wax are efficacious.
For more efficient drying at
elevated temperatures, the
vacuum apparatus (Fig. 48(A)) is
often used. The sample to be
dried is placed in an inner tube
surrounded by a heating jacket.
The latter is connected above to
a water-condenser and below to
a flask which contains a liquid of
appropriate boiling-point. The
inner tube is connected to a
water- pump. A more satisfactory
'pistol' (Fig. 48(6)) consists
of a wide glass tube A closed at
each end by ground-glass caps.
The tube is fitted with a two-
way tap, so that B can be FIG.
used for evacuating the tube,
and the capillary tube C for the subsequent re-entrance of air. The
boat D contains the drying-agent (e.g., P4O10), and a pad of glass-wool
E is held in position as shown. The material to be dried (usually in an
open specimen tube) is placed in the smaller boat F. Air should be
METHODS AND MANIPULATION 69
admitted into the evacuated tube only through the capillary tube C to
ensure a gentle stream of air: the pad E provides an extra safeguard
against material in D being swept towards F. The heating-element G
allows the tube to be heated electrically to any required thermostatically-
controlled temperature. This 'drying pistol' has obvious advantages
over that in Fig. 48(A).

FIG. 48(3).

Evaporation. Very small evaporating basins of the conventional


type may be used. Such a procedure, however, often results in the
condensation of moisture. A more
efficient method consists in drawing
CaCI 2 tube a stream of dry air over the surface of
the liquid (Fig. 49), or alternatively
in blowing air from the compressed
air mains over the liquid.
tower end of tube 7IJI[V Sublimation. This is a most
drawn to ~^^^ f [JJ] \ useful process for small-scale work
capillary t>oint^\-~*y ) as the losses are comparatively small.
This can be performed: (a) In a long
P narrow tube sealed at one end. The
IG< 49
* material is shaken to the closed end
of the tube, which is then inserted horizontally in a metal-heating block
(Fig. 50); (b) In the "cold-finger'* device (Fig. 35, p. 62).
Identification of Gases. The apparatus (Fig. SI(A)) consists of a
glass bulb B with drawn-out open ends, and fitting snugly on to the
rim of a test-tube. Before testing for a gas, a drop of the reagent is
drawn into the lower end of the bulb, which is then placed on the tube
in which the gas is being evolved. On removing the bulb and examining
the reagent against a suitable background, significant colour changes
or the formation of a precipitate in the reagent can be detected.
Vapours which can be readily condensed (e.g., chloroform, aniline,
nitro-benzene, etc.) are readily detected by the device shown in Fig. 5 I(B).
It is essentially a "cold finger" with a deep indentation or well at the
lower end. In this way two or three drops of liquid can easily be col-
lected and removed by a capillary tube for qualitative tests.
Weighing and measurements. The rough balances used for
macro-scale preparative work are not adequate for semi-micro pre-
parations. For the latter purpose, ordinary analytical balances should
PRACTICAL ORGANIC CHEMISTRY
be used. Small nickel spatulas of suitable size and design are now
available for small-scale work. Small forceps are also almost indis-
pensable.
The greatest quantitative errors in semi-micro work arise in connec-
tion with the measurement of liquids. For this reason the use of micro-
burettes and graduated dropping-tubes is essential (c/. pp. 59-60).

fOcm.

FIG. 50. FIG. SI(A).


Molecular Weight Determinations. Details of the determination
of molecular weights on a semi-micro scale by the Freezing-point
method are given on p. 436, and by the Boiling-point method on p. 440.
PREPARATIONS. By employing suitable apparatus as described above, the
student is enabled to carry out the following semi-micro preparations.
Copper acetate (p. 75)
Iodoform (p. 92)
Ethyl acetate (p. 97) and Hydrolysis of Ethyl acetate (p. ioo)
Acetanilide (p. 107) and Hydrolysis of Acetanilide (p. 108)
2-Naphthyl acetate (p. no)
Oxamide (p. 118)
Benzamide (p. 119)
Mercury benzamide (p. 120)
Glucosazone (p. 137)
Nitrobenzene (p. 157)
in-Dinitrobenzene (p. 158, -j^th scale given)
Aniline (p. 164)
m-Nitroaniline (p. 168, -^th scale given)
/>-Bromoacetanilide (p. 166)
/>-Nitroacetanilide (p. 167, lth scale given)
/>-Nitroaniline (p. 168, -£th scale given)
Chlorobenzene (p. 189, jth scale given)
Sulphanilamide (p. 181, -pytn scale given)
Diphenylnitrosoamine (p. 203)
Benzeneazo-2-naphthol (p. 210, 21OtH scale given)
Benzaldehyde phenylhydrazone (p. 229)
Benzylidene-aniline (p. 230)
METHODS AND MANIPULATION 71
Dibenzal-acetone (p. 231)
Benzoin (p. 233, poth scale given)
Benzil (p. 234), i^th scale given)
Benzil osazone (p. 234)
Phenyl benzoate (p. 244) and Hydrolysis of phenyl benzoate (p. 244)
Benzanilide (p. 245) and Hydrolysis of benzanilide (p. 246)
Benzyl />-nitrobenzoate (p. 246)
Methyl 3,5-dinitrobenzoate (p. 247)
Phenyl toluene-/>-sulphonate (p. 249)
Acetophenone (p. 255)
Acetophenone phenylhydrazone (p. 257)
Acetophenone sernicarbazone (p. 258)
Anthraquinone (p. 259)
Triphenyl carbinol (p. 285)
The preparations of all the derivatives, and all the hydrolyses of esters,
anilides, etc., described in Part III, provide excellent practice in semi-micro
manipulation.
The semi-micro scale is particularly suitable for students who wish
to carry out a succession of syntheses from one starting material. For
this purpose the following conversions are recommended.
(a) Benzene->nitrobenzene -^-aniline ->acetanilide->/>-acetamidobenzenesuI-
phonyl chloride ->/)-acetamidobenzenesulphonarnide ->sulphanilamide.
(b) Benzene-*acetanilide (as in (a))^/>-nitroacetanilide-*/>-nitroaniline.
(c) Benzene->aniline (as in (0))->benzenediazonium chloride^-benzeneazo-
2-naphthol.
(d) Benzene ^benzenediazonium chloride (as in (c))->chlorobenzene.
(e) Benzoic acid-*3,5-dinitrobenzoic acid-*3,5-dinitrobenzcyl chloride.
(/) Benzene->aniline (as in (fl))->2,4,6-tribromoaniline^i,3,5-tribromoben-
zene.

In each set of reactions, it is of course necessary to employ sufficient


of the starting material to ensure that the final product will be not less
than o* i g. for a solid and i ml. for a liquid.
STANDARD SEMI-MICRO EQUIPMENT. The authors have found, during
many years, that a student provided with the following basic semi-
micro equipment will be enabled to carry out the majority of the small
preparations described in this book.
Apparatus contained in a 14" X 5" X 3 f * box
X 50 ml. Round-bottomed flask.
X io and 1 X 5 ml. Conical flasks.
X 15 ml. Pear-shaped flask. (Fig. ZQ(A).)
X 15 ml. Pear-shaped distillation flask with condenser attached. (Fig. 36.)
X 15 ml. Pear-shaped distillation flask. (Fig. 37.)
X 7* Liebig type condenser. (C/. Fig. S(B).)
X 4* "Cold finger" type condenser. (Fig. 35.)
72 PRACTICAL ORGANIC CHEMISTRY
1 X 4* Filter tube. (Fig. 45.)
2 X i" Analytical funnels. (Fig. 46.)
1 X 5 * Cylindrical separating funnel with tap. (Fig. i6(A).)
i X 2 ml. Graduated pipette with rubber filler. (Fig. SO(A).)
i X 5^* Glass tube receiver with sloping side arm. (As in Fig. 37.)
i X 2\* Receiving tube. (Fig. 29(6).)
i X Glass "filtration nail". (Fig. 46.)
1 XHirsch funnel (2" diameter). (C, Fig. 4, p. 10.)
2 X Glass stirring rods.
2 X Semi-micro clamps.
i X Semi-micro Bunsen burner.
i x Glass bulb for gas identification tests. (Fig. SI(A).)
In addition each student will require a lightweight 14^ retort stand.
The following apparatus is desirable but not essential,
i X 50 ml. Kjeldahl flask. (Fig. 44.)
i xLiebig type condenser with side condenser attached. (Fig. 38»)
PART II
PREPARATIONS*
The Oxidation of Ethanol.
Ethanol, being a typical primary alcohol containing the -CH 2 OH group,
gives on oxidation first acetaldehyde and then acetic acid. This process, when
carried out by an aqueous oxidising agent, probably consists in the direct
O - - - ^u
CH8CH8OH > CH 3 CH(OH) 2 > CH3COOH
Ethanol. ! -H 2 O Acetic Acid.
CH8CHO
Acetaldehyde.
addition of oxygen to the ethanol to give the dihydroxy-derivative, CH3CH(OH)2;
the latter is unstable and readily loses water, e.g., on warming, to give acetalde-
hyde, while in the presence of an excess of the oxidising agent it loses two atoms
of hydrogen to give acetic acid. It is known that acetaldehyde, when dissolved in
water, partly reforms the dihydroxy-compound, a process which occurs very
readily with chloral or trichloro-acetaldehyde, CCl3CHO, which forms a stable
"hydrate," CCl8CH(OH)2.
The oxidising agent used for the preparation of both acetaldehyde and acetic
acid is a mixture of sodium dichromate and sulphuric acid, but the conditions of
the experiment are changed according to the product required. For the prepara-
tion of acetaldehyde, a mixture of aqueous sodium dichromate and ethanol is
added gradually to hot dilute sulphuric acid: just sufficient of the dichromate-
sulphuric acid mixture is thus produced to oxidise the added ethanol to acetalde-
hyde, which is rapidly distilled off from the reaction mixture. Acetaldehyde is
thus produced in moderate yield, although in spite of the above precautions
part of the aldehyde undergoes further oxidation to acetic acid. A further loss is
occasioned by the condensation of some of the aldehyde with the unchanged
ethanol under the influence of the sulphuric acid to give acetal: this loss is small,

CH 3 CHO + 2HOC 2 H 5 -> CH 3 CH(OC 2 H 5 ), -f H 2 O


however, as the reaction reaches an equilibrium and much of the regenerated
aldehyde escapes by volatilisation.
Pure acetaldehyde is extremely volatile, having b.p. 21°, and its isolation is
therefore difficult: hence only the preparation of an aqueous solution is described
below.
To prepare acetic acid, aqueous ethanol is added gradually to a hot mixture
of aqueous sodium dichromate and sulphuric acid. The oxidising mixture is
now always in excess, and therefore the oxidation proceeds as far as possible;
moreover, the reaction is carried out under reflux, so that any acetaldehyde
which volatilises is returned to the oxidising mixture. Hence the final product
contains only a small amount of acetaldehyde.
* In most of these preparations, the corks or rubber-bungs can be replaced
by ground-glass joints (pp. 42-47).
73
74 PRACTICAL ORGANIC CHEMISTRY
To prepare pure acetic acid (glacial acetic acid), the crude aqueous product
is converted into the sodium salt, the latter dehydrated by fusionf and then
heated with concentrated sulphuric acid: anhydrous acetic acid, b.p. 118°, distils
over. Only the preparation of aqueous acetic acid and of crystalline copper
acetate is described below.
Technically, acetaldehyde is mainly made by the oxidation of ethylene using
a CuCl 2 /PdCl 2 catalyst system. Although some acetic acid is still prepared by
the catalytic oxidation of acetaldehyde, the main process is the catalytic oxidation
of paraffins, usually w-butane.
Acetaldehyde, CH3CHO, in Aqueous Solution.
Required: Ethanol, 40 ml.; sodium dichromate, 50 g.; sul-
phuric acid, 17 ml.
Fit a 500 ml. bolt-head flask F with a well-fitting cork which is
free from flaws, and which carries a dropping-funnel D and a
delivery tube (or " knee-tube") T, the latter being connected
to a water-condenser C (Fig. 52). Attach an adaptor A to the
lower end of the condenser. (Alternatively, use a ground-glass
flask (Fig. 22(A), p. 43) with a distillation-head (Fig. 22(F)): the
dropping-funnel can be fitted into the distillation-head, the side-
arm of which is connected to a condenser as in Fig. 23(0), p. 45.)

Place 50 ml. of water in the flask F, and then add slowly with
shaking 17 ml. (31-5 g.) of concentrated sulphuric acid: finally
add some fragments of unglazed porcelain, and replace the flask.
Dissolve 50 g. of coarsely crushed sodium dichromate* in
* Sodium dichromate is used instead of the potassium salt because it is far
more soluble in water, and is not precipitated from its aqueous solution by
addition of the ethanol. It is also cheaper than the potassium salt, but has the
disadvantage of being deliquescent.
t Cf. p. 117.
PREPARATIONS 75
50 ml. water contained in a small beaker, add 40 ml. (32-5 g.)
of ethanol, and then place the well-stirred mixture in the drop-
ping-funnel. Ensure that a rapid stream of cold water is passing
through the condenser and that the adaptor A dips into a ioo ml.
conical flask which is surrounded with ice-water. Now heat the
dilute acid in the flask until it starts to boil gently, and then
remove the flame and run the dichromate solution very slowly
into the flask. Directly the ethanolic dichromate solution enters
the hot acid, a vigorous reaction occurs, and a mixture of acetalde-
hyde and water, containing a little acetic acid, begins to distil
over: meanwhile the reaction mixture becomes green owing to
reduction of the dichromate. The addition of the dichromate
solution should take about 20 minutes: towards the end of this
time it will be necessary to replace the flame under the flask to
maintain gentle boiling. When the addition of the dichromate
solution is complete, a moderately concentrated aqueous solution
of acetaldehyde will have collected in the conical receiver.
Note cautiously the characteristic odour of acetaldehyde which
this solution possesses. Then with the solution carry out the
following general tests for aldehydes described on p. 341: Test
No. i (SchifFs reagent), No. 3 (Action of sodium hydroxide), No.
4 (Reduction of ammoniacal silver nitrate). Finally perform the
two special tests for acetaldehyde given on p. 344 (Nitroprusside
test and the Iodoform reaction).
Pure acetaldehyde is a colourless volatile liquid, of b.p. 21°:
freely soluble in water, ethanol and ether.
It should be emphasised that the above experiment serves solely to illustrate
the oxidation of ethanol to acetaldehyde: the yield is never high, although it may
be increased by blowing carbon dioxide through the solution during the oxida-
tion in order to remove the acetaldehyde as fast as it is formed. For an efficient
production of acetaldehyde from ethanol the latter is catalytically dehydro-
genated by passing it over copper at 250-300° in an apparatus designed so that
unchanged ethanol is separated from the aldehyde and circulated again over the
catalyst.

Acetic Acid, CH3COOH, in Aqueous Solution, and


crystalline Cupric Acetate, (CH3COO)2Cu5H2O. (Semi-
micro scale).
Required: Sulphuric acid, 3-3 ml.; sodium dichromate, 3-5 g.; ethanol,
I »5 ml.; copper carbonate, 1-5 g.
Fit a 50 ml. bolt-head flask F (Fig. 53) with a reflux water-condenser
C, to the top of which a dropping-funnel D is fixed by means of a
cork having a vertical V-shaped groove G cut or filed in the side to
76 PRACTICAL ORGANIC CHEMISTRY
allow subsequent escape of air. Place 5 ml. of water in the flask and
then add 3-3 ml. (6-1 g.) of concentrated sulphuric acid slowly with
shaking: finally add 3-5 g. of coarsely crushed sodium dichromate and
some fragments of unglazed porcelain. The dichromate
rapidly dissolves in the acid, which has become hot dur- "
ing the preliminary dilution. Place in the dropping-
funnel a mixture of 1-5 ml. (1-2 g.) of ethanol and 6 ml.
of water, and allow it to fall slowly drop by drop down
the condenser into the oxidation mixture. A vigorous
reaction occurs and the mixture becomes green owing
to the formation of chromic sulphate, Cr2(SOJ3. At
frequent intervals* during the addition of the ethanol,
mix the contents of the flask by vigorous shaking. When
the addition is complete and the reaction has subsided,
heat the flask on a boiling water-bath for 15 minutes.
Then detach and reverse the condenser, and reconnect
it to the flask through a knee-tube for direct distillation,
as shown in Fig. 60, p. ioi, or Fig. 23(0), p.45. Distil
the mixture, by direct heating over a gauze, until about
8 ml. of distillate have been collected. Acetic acid is
volatile in steam and an aqueous solution of the acid,
containing, however, some acetaldehyde, is thus ob-
tained. With a very small portion of this solution,
perform the tests for acetic acid given on p. 347.
Place all but 0-5 ml. of the remainder of the distillate
-Water
in a moderately large evaporating-basin, add about 2
ml. of water (to keep the copper acetate subsequently
in solution) and then heat gently on a sand-bath
until the solution just begins to boil: then without
delay add 1-5 g. of powdered copper carbonate cau-
tiously, in small quantities at a time, to the well-
stirred hot solution until no further evolution of car-
bon dioxide occurs. Filter the mixture at the pump,
using a Buchner funnel and flask which have been
preheated by the filtration of some boiling distilled FIG. 53.
water: finally wash the residue of excess carbonate on
the filter with about i ml. of hot water, allowing the wash-water to
join the clear blue filtrate. Transfer the latter to an evaporating-basin,
and add the 0-5 ml. of original distillate which has been kept in reserve:
this prevents the subsequent formation of basic copper acetate. Now
evaporate the solution on a water-bathf until crystals begin to appear
on the surface. If the solution is now chilled in ice-water, a crop of
small crystals of copper acetate is rapidly obtained: if, however, the
• If the contents of the flask are not thoroughly mixed at this stage, an explo-
sion may occur during the subsequent distillation.
t The solution must not be concentrated by direct boiling, since copper
acetate in these circumstances undergoes hydrolysis and gives a precipitate of
cupric oxide.
PREPARATIONS 77
solution is allowed to cool slowly (and preferably allowed to stand over-
night), a crop of large, well-formed and very beautiful crystals results.
In either case, filter off the crystals at the pump, wash rapidly with a
small quantity of distilled water, drain thoroughly, and dry in an
atmospheric calcium chloride desiccator to avoid dehydration of the
crystals. By further evaporation of the filtrate, a second but less pure
crop of crystals may be obtained.
For reactions of acetic acid and acetates, see p. 347.
The Interaction of Ethanol and Sulphuric Acid.
Three compounds may be formed by the interaction of ethanol and sulphuric
acid, according to the experimental conditions:
(1) When concentrated sulphuric acid is added to ethanol, the mixture
becomes hot owing to the formation of ethyl hydrogen sulphate, the yield of
which is increased if the mixture is then gently boiled under reflux:
C2H5OH + H2SO4 -> C2H5HSO4 + H 2 O
(2) If the mixture contains an excess of ethanol, and is heated to 140°, the
ethyl hydrogen sulphate reacts with the ethanol, giving diethyl ether And
regenerating the sulphuric acid:
C 2 H 5 HSO 4 -f HOC 2 H 5 -> C 2 H 5 OC 2 H 5 + H 2 SO 4
(3) If the mixture contains a considerable excess of sulphuric acid and is
heated to 160-170°, the ethyl hydrogen sulphate breaks down, giving ethylene
and again regenerating the sulphuric acid.
C2H5HSO4 = C1H4 + H2SO4
The mechanism of the formation of these three compounds is based on the
initial reaction between ethanol and a strong acid such as sulphuric acid, which
involves protonation of the ethanolic oxygen to form the ion (I).
+
CH 3 CH 2 OH r H 2 SO 4 -^ CH 3 CH 2 -OH [- HSO 4
(I) H
This ion (I) can react in three ways, according to the conditions.
(a) reaction with the HSO 4 may give ethyl hydrogen sulphate

CH 3 CH-OH -f HSO 4 - CH 3 CH 2 OSO 3 H - H 2 O


H
(b) reaction with ethanol gives diethyl ether
H- -L-

CH 3 CH 2 -OH - CH 3 CHoOH -~ CH 3 CH 2 OCH 2 CH n H 2 O •- H


H
(c) dehydration gives ethylene

CH3CHoOH-CH, -CH, H,() H


H
78 PRACTICAL ORGANIC CHEMISTRY
Potassium Ethyl Sulphate. KC2H5SO4.
Pure ethyl hydrogen sulphate is difficult to prepare, as it is an oily liquid,
very soluble in water, and easily hydrolysed. It is therefore usually isolated
as the potassium salt, since potassium ethyl sulphate crystallises well from
water, and is not readily hydrolysed in neutral or weakly alkaline solution.
To prepare the potassium salt, the mixture of ethanol and sulphuric acid is
boiled under reflux, cooled, and treated with an excess of calcium carbonate.
2C 2 H 6 HSO 4 + CaCO, = Ca(C2H6SO4), + CO2 + H2O
The ethyl hydrogen sulphate is thus converted into the soluble calcium ethyl
sulphate, whilst the excess of sulphuric acid is removed as insoluble calcium
sulphate. The aqueous filtrate is then mixed with just sufficient potassium
carbonate to give potassium ethyl sulphate, the insoluble calcium carbonate
being now filtered off.
Ca(C2H6SOJ1 + K,CO, = 2KC2H6SO4 + CaCO,.
The solution of potassium ethyl sulphate can be concentrated on the water-
bath without appreciable hydrolysis, and the sulphate finally crystallised out.
Required: Rectified spirit, 20 ml.; sulphuric acid, 8 ml. (15 g.);
calcium carbonate, 12 g.
Place 20 ml. (16 g.) of rectified spirit in a ioo ml. round-
bottomed flask, and slowly add* 8 ml. (15 g.) of concentrated
sulphuric acid, keeping the liquid in the flask well shaken through-
out the addition to ensure thorough mixing. Fit a reflux water-
condenser to the flask, and heat the latter on a gauze so that the
mixture boils gently for 45 minutes. Then cool the product and
pour it into ioo ml. of cold water contained in a large (6-inch)
evaporating-basin or in a shallow earthenware dish. Now add
I2g. of finely powdered calcium carbonate with stirring to the
acid solution. It is essential to add the calcium carbonate as a
fine stream of powder, and to stir the latter immediately into the
bulk of the solution: for this purpose, it is best to sift the carbonate
through a fine sieve directly into the liquid, or alternatively to
add it from a spatula, tapping the latter gently over the liquid to
ensure steady addition of the finely powdered chalk. If the
carbonate is added carelessly several grams at a time, it becomes
rapidly covered with insoluble calcium sulphate, which protects it
from further reaction: in these circumstances, at least 10 times
the theoretical quantity of the carbonate may be required and the
evolution of carbon dioxide may continue for several hours.
The addition of the calcium carbonate should take about 20
* The mixture of ethanol and concentrated sulphuric acid required in this and
several subsequent preparations should always be prepared by adding the
heavy acid to the ethanol. If the ethanol is added to the acid, it will tend to
float on the surface of the acid, and the heat generated at the interface may
blow the upper liquid out of the flask
PREPARATIONS 79
minutes, and the well-stirred mixture should finally be neutral to
litmus-paper. Now heat the mixture on a water-bath, using a
thermometer as a stirrer, until the temperature reaches 60°, and
then filter at the pump through a wide Buchner funnel: at this
temperature, filtration should be rapid. Finally wash the residue
of calcium sulphate on the filter with a small quantity of hot
water, adding the wash-water to the main filtrate. In order to
convert the calcium ethyl sulphate to potassium ethyl sulphate,
add a concentrated aqueous solution of potassium carbonate
cautiously drop by drop to the well-stirred filtrate until a drop of
the latter withdrawn on a glass rod is just sufficiently alkaline to
turn red litmus-paper blue. Then filter the solution at the pump,
and wash the residual calcium carbonate again with a small
quantity of water. Evaporate the filtrate on a water-bath until
a drop withdrawn on a rod crystallises on cooling: then allow
the solution to stand until almost cold, and finally chill it
thoroughly in ice-water. (If the ice-water cooling is omitted,
large well-developed colourless crystals of potassium ethyl
sulphate will finally separate.) Filter off the crystals at the pump,
drain, and dry over calcium chloride in a desiccator.
Yield, about 6g. To obtain a second (but necessarily less
pure) crop of the sulphate, evaporate the filtrate further on the
water-bath, and cool as before.
Hydrolysis of Potassium Ethyl Sulphate. Dissolve about i g.
of the crystals in about 4 ml. of cold distilled water, and divide the
solution into two portions, (a) To one portion, add barium chloride
solution. If pure potassium ethyl sulphate were used, no precipitate
should now form, as barium ethyl sulphate is soluble in water. Actually
however, almost all samples of potassium ethyl sulphate contain
traces of potassium hydrogen sulphate formed by slight hydrolysis of
the ethyl compound during the evaporation of its solution, and barium
chloride almost invariably gives a faint precipitate of barium sulphate.
(b) To the second portion, add 2-3 drops of concentrated hydrochloric
acid, and boil the mixture gently for about one minute. Cool, add
distilled water if necessary until the solution has its former volume, and
then add barium chloride as before. A markedly heavier precipitate of
barium sulphate separates. The hydrolysis of the potassium ethyl
sulphate is hastened considerably by the presence of the free acid:
caustic alkalis have a similar, but not quite so rapid an effect.
Diethyl Ether.* (C 2 H 6 ) 2 O.
Required: Rectified spirit or ethanol, 95 ml.; sulphuric acid,
40 ml.
Assemble the apparatus shown in Fig. 54. Into the neck of
* The preparation of ether is described here because this is chemically its
logical position. It is advisable, however, for students to defer its preparation
8o PRACTICAL ORGANIC CHEMISTRY
the distilling- flask A (of about 450 ml. capacity) are fitted a thistle-
funnel F and a thermometer T, both reaching down to the bottom
of A. The dropping-funnel D is then securely fitted by a cork
into the mouth of the thistle-funnel as shown, so that the ethanol
subsequently dropping from D can be clearly seen. To the flask
A is fitted a double-surface condenser C, and to the latter in turn
a Buchner flask B to act as receiver. To the side-arm of B is
fitted a length of rubber tubing leading well below the level of
the bench, so that any ether vapour escaping condensation cannot
return to the neighbourhood of A. (Alternatively, use a ground-
glass flask (Fig. 22(A), p. 43) carrying a three-necked adaptor
(Fig. 22(j)). The thermometer can then be fitted through the
central neck, the dropping-funnel through the left-hand neck,
and the condenser joined through an adaptor (Fig. 22 (E)) to the
right-hand neck.)

FIG. 54.

First place about 5 g. of clean dry sand in A, and then 45 ml.


(36 g-) °f rectified spirit: cool the flask in ice-water and
cautiously add 40 ml. (74 g.) of concentrated sulphuric acid,
shaking the mixture thoroughly during the addition to ensure a
until they have had some experience in the manipulation, and particularly the
distillation, of ether, such as its use for the extraction of aniline (p. 163), where
full details and precautions are given.
PREPARATIONS 81
homogeneous product. Then reassemble the apparatus, taking
care that the lower end of the thistle-funnel F now7 reaches down
to the bottom of the liquid in the flask and that the bulb of the
thermometer is completely immersed. Place 50 ml. (40 g.) of
rectified spirit in the funnel D, and cool the receiver B in a pan of
ice-water. Heat the flask A over a gauze by means of a small
Bunsen flame until the temperature of the liquid reaches 140-145°:
owing to the presence of the sand steady boiling now occurs, and
ether begins to distil over. Now allow the ethanol in D to fall
drop by drop into the thistle-funnel F at approximately the
same speed as that at which the crude ether distils over: in this
way the total addition of the ethanol from D should take about
i hour. Then continue heating A (still maintaining the tempera-
ture at 140-145°) until no more ether distils over, i.e., for about
a further 15 minutes. Turn out the gas, and then pour the
distillate into a separating-funnel and shake it with about 25 ml.
of 10% aqueous sodium hydroxide solution: this removes both
sulphur dioxide and some of the unchanged ethanol from the
ether. Run off and reject the lower aqueous layer, and then re-
peat the extraction with a fresh quantity of sodium hydroxide
solution. Again run off the alkaline layer, transfer the ether to a
small conical flask and dry it with an ample quantity of granular
calcium chloride for at least 30 minutes. (The calcium chloride
removes both water and any residual ethanol.)
Now filter the ether through a fluted filter-paper directly into
a ioo ml. distilling-flask, and then equip the latter with a 100°
thermometer and a double-surface condenser: to the end of the
latter attach a receiver with a rubber delivery-tube precisely as
before. Place the flask cautiously in a water-bath, the contents
of which have previously been heated to about 6o° at some
distance from the apparatus: arrange the depth of the flask in
the water-bath so that the ether distils slowly over. Collect the
fraction boiling between 34-39°. Yield, 25 g. (35 ml.). Not
more than a very small residue of ethanol should remain in the
flask.
Diethyl ether is a mobile, colourless liquid having b.p. 35° and
d, 0-720. It has a characteristic odour, and a burning taste. It is
used chiefly as a solvent, and was formerly widely used as an
anaesthetic; owing to its chemical non-reactivity, it is very seldom
used actually as a reagent, except in the preparation of Grignard
reagents (p. 280) where probably its chemical properties reinforce
its solvent action.
Very great care should always be taken when manipulating
82 PRACTICAL ORGANIC CHEMISTRY
ether, particularly when it is being distilled. The liquid itself
is very readily inflammable, and in addition the vapour forms
with air a heavy and highly explosive mixture, which may roll
along the laboratory bench for surprising distances, and still
be capable of exploding when it comes in contact with a flame,
the explosion at once travelling back towards the origin of the
vapour.
For Williamson's Method for the preparation of ethers, see p. 103.

Pure Ether. Pure ether (entirely free in particular from water) is


frequently required in the laboratory, and especially for the preparation
and use of Grignard reagents. It is best prepared in quantity for
classes by adding an ample quantity of granular calcium chloride to a
"Winchester" bottle of technical ether, and allowing the mixture to
stand for at least 24 hours, preferably with occasional shaking. The
greater part of the water and
ethanol present in the ether is thus
removed. The ether should now
be filtered through a large fluted
filter-paper into another clean dry
Winchester bottle. About 25 g.
of sodium are now pressed as fine |cf
wire directly into the ether. For
this purpose, a sodium press is
used (Fig. 55). This consists
essentially of a heavy iron stand S
carrying a plunger P, which can
be screwed down so that its end
fits snugly into an iron cup C,
which has a small hole at its base.
(A number of cups, having holes FIG. 55.
of different diameters, is usually
available for alternative use.) The cup C is nearly filled with lumps
of sodium, and the plunger is then screwed steadily down, while (in
this case) the Winchester bottle of ether is held immediately below C:
the sodium is thus forced as fine wire directly into the ether, and
exposure to the air reduced to a minimum.
The Winchester bottle should then be closed by a rubber stopper
carrying a calcium chloride tube (to allow escape of hydrogen) and the
ether allowed to stand for a further 24 hours. It should then be
decanted into a large distilling-flask, a few small pieces of freshly cut
sodium preferably added, and the flask connected with a double-surface
water-condenser having a receiver cooled in ice-water. Ether in these
quantities should always be distilled in a fume-cupboard having an
efficient draught, so that there is no possibility of any uncondensed
vapour escaping into the laboratory. The flask itself should be heated
PREPARATIONS 83
by steam. If steam is not laid on in the fume-cupboard, it should be
generated outside the cupboard in the usual steam-can (Fig. 15, p. 33)
and then led into the cupboard through a length of soft metal "compo"
tubing. The flask is supported on the usual concentric metal rings
over an empty water-bath: a hole is punched in one of the outer rings,
and then the compo tubing is led down throught this hole into the bath,
and the extreme end of the tubing turned up so that the jet of steam
strikes directly upwards on to the base of the flask. If the fume-
cupboard has a vigorous draught induced by an electric motor, large
quantities of the ether can thus be safely distilled, and an ordinary
bottle can be used as a receiver, the end of the condenser being fitted
into the neck of the bottle and held firmly in position by a plug of
cotton-wool. If a large Buchner flask is used as a receiver, the
rubber delivery tube (as shown in Fig. 54, p. 8o, and in Fig. 23(E), p. 45)
is of course required.
In very hot weather, the condenser water should first be chilled by
passing it through a tall spiral of soft metal "compo" tubing immersed
in a bucket of ice-water.
Ether so obtained is anhydrous, and almost entirely free from other
impurities. On standing, however, it undergoes slight atmospheric
oxidation, with the formation of traces of diethyl peroxide, (C2H5J2O2.*
The formation of this peroxide can be largely checked, however, by
storing the distilled ether over fresh sodium wire, preferably in the dark.

Ethylene. C2H4.
Required: Rectified spirit, 20 ml.; sulphuric acid, 40 ml.
Assemble the apparatus shown in Fig. 56. F is a 200 ml.
flat-bottomed flask supported on a sand-bath and connected by
a glass delivery-tube to the wash-bottle B, which is about two-
thirds full of io % aqueous sodium hydroxide solution. A second
delivery-tube leads from B into a beehive stand (or between two
earthenware tiles placed side by side) in a pneumatic trough T
containing water.
Place 20 ml. (16 g.) of rectified spirit in F, and add slowly,
with cooling and shaking, 40 ml. (74 g.) of concentrated
sulphuric acid. Then add about 2-3 g. of clean dry sand, to
ensure a steady evolution of ethylene subsequently. Connect
up the apparatus and heat F over the sand-bath as shown.
* Consequently traces of these unstable peroxides are present in samples of
all the lower aliphatic ethers unless the samples have been freshly distilled.
If these ethers when being distilled are heated on, for example, an electric
heater, the final residue of peroxide may become sufficiently hot to explode
violently. The use of a water-bath for heating, as described above, decreases
considerably both the risk of the ether catching fire and of the peroxide
exploding.
Peroxides can usually be completely removed from a sample of ether by
thorough shaking with aqueous potassium permanganate solution.
84 PRACTICAL ORGANIC CHEMISTRY
The liquid becomes progressively darker in colour, and then
effervesces gently as ethylene is evolved. Allow the gas to escape
from the delivery-tube in T for several minutes in order to sweep
out the air in F and B. Now fill a test-tube with water, close it
with the finger, and invert the tube in the water in T over the
delivery-tube so that a sample of the gas collects in the tube.
Close the tube again with the finger, and then light the gas at a
Bunsen burner at a safe distance from the apparatus. If the tube
contains pure ethylene, the latter burns with a clear pale blue
(almost invisible) flame: if the ethylene still contains air, the
mixture in the test-tube ignites with a sharp report. Allow the

FIG. 56.
gas to escape from the delivery-tube in T until a sample tested in
this way proves to be pure ethylene. Then collect 3-4 gas-jars of
ethylene, closing each one under water with a slightly greased
glass plate. Since appreciable quantities of. sulphur dioxide are
evolved in F during the later stages of the reaction, disconnect
the delivery-tube joining F to B, and then turn out the gas.
Carry out the following tests with the jars of ethylene.
(1) Odour. Smell the contents of one of the jars. The
ethylene has a characteristic sweetish odour.
Ethylene when deeply inhaled produces temporary anaesthesia which
is almost devoid of unpleasant after-effects; hence it has been used for
dental surgery, minor operations, etc.
(2) Bromine. Slip slightly to one side the glass plate covering
one jar of ethylene, add 2-3 ml. of bromine water (preparation,
p. 525), restore the glass plate in position, and then shake the jar
vigorously. The colour of the bromine rapidly disappears as
i,2-dibromoethane is formed. Note that owing to the absorption
C 2 H 4 + Br 2 = C 2 H 4 Br 2
of ethylene, a partial vacuum now exists in the jar.
PREPARATIONS gs
(3) Alkaline Potassium Permanganate. Add similarly to a
second jar 1-2 ml. of very dilute aqueous potassium permanganate
solution to which an equal volume of sodium carbonate solution
has previously been added. On shaking as before, the purple
colour of the permanganate is replaced by the green colour of
potassium manganate, K 2 MnO 4 ; further reduction ultimately
causes the green manganate to be replaced by a brown precipitate
of manganese dioxide. Note that a partial vacuum again exists
owing to the absorption of ethylene.
In this reaction the ethylene is oxidised to ethylene glycol, C2H4(OH)1.
C 4 H 4 -f H 2 O + O = C8H4(OH),
If a solution of potassium permanganate containing dilute sulphuric acid
is used, the purple colour disappears and the solution ultimately becomes
2KMnO 4 H- 3H 2 SO 4 = K8SO4 + 2MnSO4 + 3H2O + sO
colourless. The use of the sodium carbonate solution, and the consequent
change in colour first to the green manganate and then to the brown manganese
dioxide, make the reagent more sensitive to observation.
Tests for Unsaturation. The above reactions are used as
the general tests for the presence of double or triple bonds
joining carbon atoms in an organic compound.
(1) The bromine test is applied first. The organic compound,
if a liquid, is treated with 2-3 drops of liquid bromine or (prefer-
ably) a solution of bromine in carbon tetrachloride: if the
organic compound is a solid, it should first be dissolved in cold
carbon tetrachloride or chloroform. The rapid absorption of the
bromine (and consequent disappearance of the red colour) is a
strong indication that the compound is unsaturated, and is there-
fore undergoing direct addition of the bromine.
Since, however, some compounds, such as aniline (p. 164),
react very rapidly with bromine by substitution, the bromine test
should whenever possible be confirmed by the alkaline perman-
ganate test.
(2) If the compound is soluble in cold water, its aqueous
solution (after neutralisation, if acidic) is shaken with a dilute
solution of potassium permanganate containing sodium car-
bonate as before. The conversion of the purple permanganate to
the green manganate or (more frequently) directly to manganese
dioxide confirms the result of the bromine test, since the alkaline
permanganate is unaffected by possible substitution reactions.
Note that many readily oxidisable compounds (e.g., aldehydes)
will also decolorise alkaline potassium permanganate in the cold.
86 PRACTICAL ORGANIC CHEMISTRY
Acetylene. C2H2.
Acetylene can be readily obtained by the action of water on calcium car-
bide: since, however, commercial calcium carbide contains traces of calcium
CaC2 -f- 2HOH = Ca(OH)8 + C 2 H 2
sulphide, phosphide and nitride, the acetylene should be purified before use.
If a specially pure sample of acetylene is required, it should be obtained by
the action of alcoholic potassium or sodium hydroxide on i,2-dibromoethane:
this reaction should be compared with that of aqueous potassium or sodium
hydroxide, which merely hydrolyses i,2-dibromoethane to ethylene glycol.
C 2 H 4 Br 2 - aKOH (ethanolic) CJI 2 -f aKBr - 2H 2 O
C 2 H 4 Br 2 + 2KOH (aqueous) = C8H4(OH)1 -f zKBr
If acetylene is required either in large quantities or in a steady regular
current for several hours, it should be obtained from a cylinder, in which the
acetylene is compressed in acetone solution. The cylinders can be purchased
and when empty can then be exchanged for refilled ones. The acetylene in
these cylinders is generated from calcium carbide, but is considerably purified
before storage in the cylinder. The acetylene before use should, however, be
passed through two wash-bottles containing water to eliminate acetone vapour:
acetylene of high purity is then obtained.
(A) FROM CALCIUM CARBIDE. Place some small lumps of
calcium carbide (about 15 g.) in a 150 ml. distilling-flask (or in
a Buchner flask of similar capacity), and fit into the neck of the
flask a tall dropping-funnel the stem of which has been drawn off
to a fine point: the stem should pass well down below the side-
arm of the flask. Connect this side-arm to a wash-bottle con-
taining 10% aqueous copper sulphate solution: the tall dropping-
funnel is thus required in order to give a sufficient "head" of
water in the funnel to force the acetylene through the wash-bottle.
Then fit to the wash-bottle a delivery-tube which'passes into a
pneumatic trough precisely as that in Fig. 56 (p. 84).
Fill the dropping-funnel with water, and allow the latter to fall
drop by drop on to the calcium carbide: acetylene is at once
generated, and on passing through the copper sulphate solution
is freed from hydrogen sulphide, etc. Allow the gas to escape
from the delivery-tube in the pneumatic trough until the issuing
gas smells markedly of acetylene. Then collect a sample of the
gas in a small test-tube precisely as described for ethylene (p. 84).
Ignite the sample at a burner placed as before at a safe distance
from the apparatus. If the air in the apparatus has not yet been
completely displaced, the sample of gas will explode with a sharp
report: if, however, the acetylene is free from air, it will burn
quietly with a very smoky flame depositing carbon in the tube, in
marked contrast to the clear flame of burning ethylene.
PREPARATIONS 87
Then collect 5-6 gas-jars filled with the acetylene, and carry
out the following tests.
(1) Odour. The gas collected in this way has a somewhat
onion-like odour, which is much less pronounced than that of the
crude gas given off directly from the carbide without subsequent
purification. Absolutely pure acetylene, however, is almost
odourless.
(2) Bromine. Slip the glass cover of a jar momentarily aside,
add 2-3 ml. of bromine water, replace the cover and shake the
contents of the jar vigorously. Note that the bromine is absorbed
only very slowly, in marked contrast to the rapid absorption by
ethylene. This slow reaction with bromine water is also in
marked contrast to the action of chlorine water, which unites with
acetylene with explosive violence. (Therefore do not attempt
this test with chlorine or chlorine water.)
(3) Alkaline Permanganate. To another jar add similarly
2-3 ml. of very dilute potassium permanganate solution con-
taining sodium carbonate. On shaking the jar the permanganate
is reduced to green manganate, although the colour of the latter is
only transient and is moreover obscured by the manganese
dioxide formed.
(4) Metallic Derivatives, (a) Cuprous Acetylide. Cu 2 C 2 .
Prepare an ammoniacal solution of cuprous chloride by first
adding dilute ammonia to 2-3 ml. of dilute copper sulphate
solution until the initial precipitate just redissolves and a clear
deep-blue solution is obtained: now add an aqueous solution of
hydroxylamine hydrochloride drop by drop with shaking until
the solution becomes first green and then completely colourless,
the cupric salt being thus reduced to the cuprous derivative.
Now add this solution to ajar of acetylene as before and shake
vigorously. A chocolate-red precipitate of cuprous acetylide is
at once formed.
(b) Silver Acetylide. Ag 2 C 2 . Add dilute ammonia drop by
drop with shaking to 2-3 ml. of silver nitrate solution until the
initial precipitate of silver oxide just redissolves.
Now add this solution to a jar of acetylene and shake. A
yellow-white precipitate of silver acetylide at once forms.
The cuprous and silver acetylides are both explosive when
dry. Therefore when these tests are completed, wash out the
gas-jars thoroughly with water.
(B)FROM 1,2-DIBROMOETHANE. Required: Powdered
potassium hydroxide, 25 g.; rectified spirit, ioo ml.; ethylene
dibromide, 15 ml. (33 g.).
88 PRACTICAL ORGANIC CHEMISTRY
To prepare pure acetylene, assemble the apparatus shown in
Fig. 57. F is a wide-necked 300 ml. bolt-head flask, to which is
fitted a double-surface reflux water-condenser C and the dropping-
funnel D. From the top of C, a delivery-tube leads down to the
pneumatic trough T, where the gas can be collected in jars in the
usual way. (Alternatively, use the apparatus shown in Fig.

FIG. 57.

p. 45.) Place ioo ml. of rectified spirit and 25 g. of powdered


potassium hydroxide in F, and boil the mixture gently under
reflux until the potash is almost entirely dissolved. Then place
15 ml. (33 g.) of i,2-dibromoethanc in D, and allow the dibro-
mide to fall drop by drop into the boiling solution in F. A
rapid reaction occurs, acetylene being generated and potassium
bromide precipitated. Test the gas issuing from the delivery-
tube in the usual way to ensure that all air has been displaced
by acetylene. Then collect the pure acetylene in gas-jars. Note
that this acetylene is almost odourless.
Ethylene can be similarly prepared by the action of ethanolic potash
on ethyl bromide, but the yield is usually very low.

Absolute Ethanol. Supplies of absolute cthanol, which is frequently


required in organic chemical work, arc now freely available commer-
cially as a result of azeotropic distillation methods. If however it should be
PREPARATIONS 89
necessary to dehydrate rectified spirit, the process can be carried out most
reliably by the use of quick-lime. The quick-lime should preferably be pre-
pared in the laboratory by heating lumps of marble strongly in a good muffle-
furnace for about 3 hours; the product, directly it cools, must be stored in
a tightly stoppered tin or bottle, although whenever possible it should be
used for dehydration immediately after its preparation. If the lime is obtained
from a dealer, it should preferably be reheated immediately before use.
The preparation of absolute ethanol in moderate quantity for classes may be
carried out as follows. Pour 3 Winchester bottles (i.e., 7-8 litres) of rectified
spirit into a 3-gallon (14-15 litre) can C (Fig. 58), add about 600 g. of the

FIG. 58.

quick-lime, and fit a double-surface reflux condenser by means of a rubber


stopper, the top of the condenser being closed with a calcium chloride tube. Place
the can in a large galvanised iron bath G about half-full of water, supporting the
can in the bath on some earthenware tiles. Heat the water-bath over a gas-ring
so that the ethanol boils gently under reflux for 6 hours. Now (preferably)
allow the apparatus to cool and stand overnight. Next day, add a further ioo g.
of quick-lime to the ethanol, and fit to the can a still-head S as shown (Fig. 58).
Reverse the condenser for distillation, and connect it to an adaptor A, which
fits directly into the bottle B in which the absolute ethanol will subsequently
be stored. Rubber stoppers must be used throughout the apparatus: that which
fits into the receiving bottle B carries a calcium chloride tube T as shown.
Now reheat the water-bath so that the ethanol distils over steadily: no "bumping"
should occur in the can. Stop the distillation when about 500 ml. of ethanol
still remain in the can.
The absolute ethanol obtained in this way should have d 15 4 l, 0-794. It is very
hygroscopic, and the bottle in which it is stored should preferably have a well-
fitting ground-glass stopper: alternatively, the bottle can be closed with a
tightly fitting rubber stopper but not with a cork, as corks contain appreciable
quantities of water.
Absolute methanol can be similarly prepared, and then has ^1Jo, 0-796.
9o PRACTICAL ORGANIC CHEMISTRY
Chloroform. CHCl3.
When chlorine is passed into boiling ethanol, both chlorination of the methyl
group and oxidation of the primary alcohol group to an aldehyde occur, giving
trichloro-acetaldehyde or chloral:
CH 3 CH 2 OH + 4C12 -> CCl3CHO r 5HC1
When chloral is treated with caustic alkali, fission of the C-C linkage occurs,
giving chloroform and a formate:
CCl3CHO -f- KOH -> CHCI 3 + HCOOK
Acetaldehyde and also many ketones, such as acetone, containing the CH 3 CO-
group behave similarly when treated with bleaching powder, chlorination of
the CH3CO- group being immediately followed by fission of the molecule by
the alkali present in the bleaching powder:
CH 3 COCH 3 -f 3C12 -> CCI 3 COCH, -f CHCl3

2CCl 3 COCH 3 -u Ca(OH), — 2CHCl 3 f (CH 3 COO) 2 Ca


The acetone method clearly gives a much cheaper product than the ethanol
method.
Required: Bleaching powder, ioo g.; acetone, 44 ml.
Place ioo g. of bleaching powder in a mortar and add 250 ml.
of water in small quantities at a time: between each addition
grind the mixture of bleaching powder and water well together
and decant the cream-like suspension through a funnel into a
i-litre flat-bottomed flask. Finally, when all the water has
thus been used, only a gritty residue remains in the mortar. Fit
the flask with an efficient reflux water-condenser, pour 44 ml.
(35 g-) °f acetone in small quantities, at a time, down the
condenser and mix by thorough shaking after each addition.
The reaction usually starts spontaneously after a few minutes,
and a bath of cold water should be available into which the
flask may be dipped if necessary to moderate the reaction.
Should the reaction show no signs of starting within 5 minutes of
the addition of the acetone, warm the flask cautiously on a boiling
water-bath until the reaction starts, and then remove it immedi-
ately. When the vigorous boiling has subsided, heat the flask on
a boiling water-bath for a further 5-10 minutes (not more) to
complete the reaction. Cool the flask in cold water (to prevent
toss of chloroform vapour whilst the apparatus is being reT
arranged) and then fit the flask with a fairly wide delivery-tube
and reverse the water-condenser for distillation (as in Fig. 59,
p. ioo, or in Fig. 23(0), p. 45). Heat the flask on a water-bath
until distillation of the chloroform is complete.
The chloroform thus obtained is usually acidic. Therefore
PREPARATIONS 9*
shake it thoroughly with dilute sodium hydroxide solution in a
separating-funnel. (If the chloroform tends to float on the alka-
line solution, it still contains appreciable quantities of acetone: in
this case the sodium hydroxide solution should be run out of the
funnel and the chloroform shaken with water to extract the acetone.
The extraction with the sodium hydroxide solution can then be
performed after the water has been removed.) Carefully run off
the heavy lower layer of chloroform into a small conical flask, dry
it over calcium chloride for 15-10 minutes, and then filter it
directly into a 75 ml. distilling-flask fitted with a clean dry water-
condenser. Distil the chloroform, collecting the fraction of b.p.
60-63°. Yield, 30 g. (20 ml.)
Chloroform is a colourless liquid, of b.p. 61° and d, 1-50. It
has a characteristic sweetish smell, and is frequently used as a
solvent in organic chemistry.
For reactions of chloroform, see p. 392.
Chloroform was formerly used in medicine as an anaesthetic. One disadvan-
tage for this purpose is the ready oxidation which chloroform undergoes on
exposure to light and air, generating the poisonous phosgene, or carbonyl
chloride, COCl2. This is counteracted by storing the liquid in dark amber-
CHCl8 + O = COCl2 + HCl.
coloured bottles, and also by the addition of about 2% of ethanol: the latter
converts the phosgene into harmless diethyl carbonate:
2C2H6OH + COCl, = (C2H6O)2CO +
In addition to chloroform, many other compounds containing the trichloro-
methyl group, Cl3C-, show marked physiological action. Thus trichloro-
acetaldehyde or chloral hydrate, Cl 3 C-CH(OH) 2 (p. 342), and trichloro-tertiary-
butanol or chloretone, Cl3C-C(CHs)2OH, are both hypnotics. Similarly,
tribromo-ethanol or avertin, Br 8 C-CH 2 OH, has strong anaesthetic properties.

Iodoform. CHI3.
The preparation of iodoform is similar to that of chloroform, of which it is
the iodine analogue. Many substances which contain either the CH3CH(OH)-
group or the CH8CO-C group when treated with potassium iodide and sodium
hypochlorite readily yield iodoform, and its formation can thus frequently
be used as a test for these groups.* Among the compounds which contain the
CH8CH(OH)- group and give iodoform are ethanol, CH 8 CH 2 OH, isopropanol,
CH3CH(OH)CH8, lactic acid, CH3CH(OH)COOH, and also acetaldehyde,
which exists in aqueous solution partly as the hydratcd form, CH8CH(OH)1:
similar compounds containing the CH3CO-C group are acetone, CH8CO-CH8,
pyruvic acid, CH8CO-COOH, and acetophenone, CH8CO-C8H5. Methanol
* For other types of compounds which give the iodoform reaction, see
H. Booth and B. C. Saunders, Chem. and Industry , 1950. 824.
92 PRACTICAL ORGANIC CHEMISTRY
does not give iodoform in these circumstances and can thus be distinguished
from ethanol.
The reactions involved are similar in both cases, and closely parallel to
those which give rise to chloroform. The sodium hypochlorite probably first
oxidises the potassium iodide to potassium hypoiodite, which then oxidises
the ethanol to acetaldehyde and then iodinates the latter to tri-iodo-
CH5CH2OH > CH3CHO ^ CI3CHO
acetaldehyde or iodal. Aqueous sodium hypochlorite always contains sodium
hydroxide, which converts the tri-iodo-acetaldehyde to iodoform and sodium
formate.
CI 3 CHO -f NaOH -> CHI 3 + HCOONa

If acetone is used there is no initial oxidation: tri-iodo-acetone is first


formed and is then converted by the sodium hydroxide to iodoform and
CI 3 COCH 3 -f NaOH -> CHI 3 + CH3COONa
sodium acetate. Iodoform is obtained more readily and in greater yield from
acetone and acetaldehyde than from ethanol, possibly because no initial oxidation
is required.
Iodoform is a disinfectant and can be used as an external antiseptic.
IODOFORM FROM ACETONE. (Semi-micro Scale.)
Required: Acetone, 0-5 ml.; 10% potassium iodide solution, 20
ml.; 10% sodium hydroxide solution, 8 ml.; zM sodium hypo-
chlorite solution, 20 ml.
Place 0-5 ml. of acetone, 20 ml. of 10% aqueous potassium
iodide solution and 8 ml. of 10% aqueous sodium hydroxide
solution in a 50 ml. conical flask, and then add 20 ml. of a
freshly prepared molar solution* of sodium hypochlorite.
Well mix the contents of the flask, when the yellow iodoform
will begin to separate almost immediately: allow the mixture to
stand at room temperature for 10 minutes, and then filter at the
pump, wash with cold water, and drain thoroughly. Yield of
crude material, 1-4 g. Recrystallise the crude iodoform from
methylated spirit. For this purpose, place the crude material in a
50 ml. round-bottomed flask fitted with a reflux water-condenser,
add a small quantity of methylated spirit, and heat to boiling
on a water-bath: then add more methylated spirit cautiously
down the condenser until all the iodoform has dissolved. Filter
the hot solution through a fluted filter-paper directly into a small
beaker or conical flask, and then cool in ice-water. The iodoform
rapidly-crystallises. Filter at the pump, drain thoroughly and
dry.
* For preparation of zM sodium hypochlorite solution, see p. 525.
PREPARATIONS 93
Iodoform forms yellow crystals, of m.p. 120°, and has a charac-
teristic odour.
For reactions of iodoform, see pp. 390-392.

Oximes.
Both aldehydes and ketones usually condense readily with free hydroxyl-
amine, HONH 2 , to give crystalline oximes:
CH 3 CHO + H 2 NOH -> CH 3 CHrNOH + H 2 O
Acetaldehyde Acetaldoxime
(CHg) 2 CO -f H 2 NOH -> (CH 3 ) 2 C:NOH + H 2 O
Acetone Acetoxime
Since hydroxylaminc is usually available only in the form of its salts, e.g., the
hydrochloride or sulphate, the aqueous solution of these salts is treated with
sodium acetate or hydroxide to liberate the base before treatment with the
aldehyde or ketone. Most oximes are weakly amphoteric in character, and may
dissolve in aqueous sodium hydroxide as the sodium salt, from which they can
be liberated by the addition of a weak acid, e.g., acetic acid.
Oximes have four important uses:
(1) Being crystalline compounds which usually have sharp melting-points,
they are used to characterise the parent aldehydes and ketones.
(2) Impure aldehydes and ketones are sometimes purified by conversion into
the corresponding oximes, and the latter after recrystallisation are then hydro-
lysed by boiling with dilute sulphuric acid:
(CH 3 ) 2 C:NOH -f H 2 O -f H 2 SO 4 = (CH3)2CO -f HONH 2 ,H 2 SO 4
The acid, by neutralising the hydroxylamine, prevents the reverse reaction
and thus causes rapid and complete hydrolysis: distillation of the final solution
then drives over the aldehyde or ketone, the hydroxylamine sulphate remaining
behind. This method must be used with care, however, as the acid may cause
the Beckmann rearrangement to occur (p. 227).
(3) Reduction gives pure primary amines:
CH,CH:NOH 4- 4H - CH 8 CH 2 NH 2 -f H 2 O
Monoethylamine
(CH 3 ) £ C:NOH + 4H = (CH,),CHNH, -f H 2 O
Isopropylamine
(4) When treated with certain reagents, the ketoximes in particular undergo
the Beckmann rearrangement to isomeric acid amides (p. 227).
For the further identification of aldehydes and ketones by phenylhydrazone
formation, see pp. 229, 257, 341, 345; by 2,4-dinitrophenylhydrazone formation,
see pp. 262, 342, 346; by semicarbazone formation, see pp. 258, 342, 346.

Acetoxime. (CH3)2C:NOH.
Required: Hydroxylamine hydrochloride, 12-5 g.; sodium
hydroxide, 7 g.; dry acetone, 12 ml.
94 PRACTICAL ORGANIC CHEMISTRY
(NOTE. The sodium hydroxide must be accurately weighed
out, for an excess will dissolve the oxime as the sodium derivative.)
Prepare a solution of 12-5 g. of hydroxylamine hydro-
chloride in 20 ml. of water contained in a ioo ml. conical flask.
Dissolve 7 g. of powdered sodium hydroxide in 20 ml. of
water, cool the solution in ice-water, and then add it to that of
the hydroxylamine hydrochloride. Place a thermometer in the
mixed solution, and chill the flask in ice-water until the tempera-
ture of the solution is between 5° and io°. Now add 12 ml.
(9*5 £•) °f dry acetone (preferably from a burette to ensure
accuracy) in small quantities so that, when the mixture is gently
shaken in the ice-water during the addition, the temperature
does not rise above 15°. The acetoxime usually starts to crystal-
lise when about half the acetone has been added. When the
addition is complete, allow the mixture to stand in ice-water for
15 minutes, and then filter off the crude acetoxime at the pump,
drain well and finally dry by pressing repeatedly between several
layers of drying-paper. The acetoxime so obtained contains
sodium chloride, but is otherwise almost pure. Yield of crude
dry material, 12-13 g.
The oxime is freely soluble in water and in most organic liquids.
Recrystallise the crude dry product from a minimum of 60-80°
petrol or (less suitably) cyclohexane: for this purpose first
determine approximately, by means of a small-scale test-tube
experiment, the minimum proportion of the hot solvent required
to dissolve the oxime from about 0-5 g. of the crude material.
Then place the bulk of the crude product in a small (ioo ml.)
round-bottomed or conical flask fitted with a reflux water-
condenser, add the required amount of the solvent and boil the
mixture on a water-bath. Then turn out the gas, and quickly
filter the hot mixture through a fluted filter-paper into a conical
flask: the sodium chloride remains on the filter, whilst the
filtrate on cooling in ice-water deposits the acetoxime as colourless
crystals. These, when filtered and dried (either by pressing between
drying-paper or by placing in an atmospheric desiccator) have m.p.
60°. Acetoxime sublimes rather readily when exposed to the air,
and rapidly when warmed or when placed in a vacuum. Hence
the necessity for an atmospheric desiccator for drying purposes.
Hydrolysis of Acetoxime. Place about i g. of the recrystallised
oxime in a small distilling-flask (50 ml.), add 10 ml. of dilute H2SO4,
and heat gently until about half the solution has distilled over. Test
(a) the aqueous distillate for acetone by the iodoform reaction (p. 346),
(b) the residual solution in the distilling-flask for hydroxylamine by
PREPARATIONS 95
cooling, making strongly alkaline, and treating with Fehling's solution.
A deep yellow precipitate of cuprous oxide results:
2HONH 2 + 4CuO = 2Cu 2 O + N2O + 3 H 2 O

Esters.
Esters may be prepared by the following methods:
(i) Directly from the corresponding acid and alcohol, in the presence of a
dehydrating agent. Thus when ethanol and acetic acid are mixed, ethyl
acetate and water are formed, but in addition an equilibrium is established.

CH 3 COOH + HOC 2 H 5 - CH 3 COOC 2 H 5 + H 2 O


If, however, concentrated sulphuric acid is present, the water is absorbed, the
back reaction prevented, and a high yield of ethyl acetate is obtained. In
practice the reaction is not so simple. It was formerly supposed that, since the
sulphuric acid is usually added to the alcohol, ethyl hydrogen sulphate and
water are formed, the latter being absorbed by the excess of sulphuric acid.
A mixture of ethanol and acetic acid is then added to the ethyl hydrogen sulphate,
C2H5OH + H2SO4 -> C 2 H 5 HSO 4 + H 2 O
whereupon the latter reacts with the organic acid to give the required ester,
liberating the sulphuric acid which at once reacts with the free alcohol, the cycle
C1H5HSO4 + CH3COOH = CH3COOC2H5 + H 2 SO 4
of operations then recurring. The process can thus continue until the sulphuric
acid becomes too dilute to furnish more ethyl hydrogen sulphate.
This method has the disadvantage that the corresponding ether is usually

C 2 H 5 HSO 4 + HOC 2 H 5 -> (C 2 H 5 ) 2 O + H 2 SO 4


formed as a by-product by the interaction of the alkyl hydrogen sulphate and
unchanged alcohol.
The mechanism of esterification of an alcohol in the presence of a mineral
acid is now considered to involve the following steps.
(1) Protonation of the carbonyl oxygen of the acid (I) to give (II), which is
attacked by the lone pair on the oxygen atom of the alcohol to give the inter-
mediate (III);

O OH Et OH Et

R-C
;: 4-
+
H^ R-C
i +
-f
/
:O ^
i +/
R-C-O
i \ I \
OH OH H OH H
(I) (II) (III)

(2) This is followed by proton transfer to give the intermediate (IV).

(3) Loss of water now gives the protonated form (V) of the ester (VI).
96 PRACTICAL ORGANIC CHEMISTRY
OH OH O
I I -H- I!
(Ill) ^=* R - C - O E t =F=^ R - C - O E t 5=^ R - C - O E t
1
+O

H H
(IV) (V) (VI)

A series of equilibria is thus established, the constituents of the mixture depen-


ding on the local conditions.
(2) The Fischer-Speier Method. In certain cases of esterification sul-
phuric acid cannot be used. Thus if the alcohol or the organic acid is
unsaturated, the sulphuric acid may add on at the unsaturated group. If the
alcohol or the acid is aromatic in type, considerable sulphonation of the
benzene ring may result. Finally, if an amino-acid, such as glycine or ammo-
acetic acid, NH 2 CH 2 COOH, is to be esterified, the amino group would also
undergo salt formation, and thus the hydrogen sulphate of aminoacetic ethyl
ester, H 8 SO^NHaCH 2 COOC 2 Hj 1 , would result, and would be very difficult to
isolate from the excess of sulphuric acid. These difficulties are overcome by the
Fischer-Speier method, in which a mixture of the alcohol and the organic acid is
gently boiled under reflux whilst a stream of dry hydrogen chloride gas is passed
in, a high yield of the ester being thus obtained. The function of the hydrogen
chloride is protonating and catalytic, since Fischer found that 5% of hydrogen
chloride in the reaction mixture gave efficient esterification. The advantages of
the Fischcr-Speier method are that the hydrogen chloride does not usually add
on to unsaturated groupings, it does not affect aromatic groups, and finally with
amino-acids gives the hydrochloride of the ester, from which excess of hydro-
gen chloride can be readily removed by direct evaporation. A further advan-
tage is that the corresponding ether is not formed as a by-product. The method
is also suitable for the preparation of esters of hydroxy-acids, e.g., lactic acid.
(3) Esters can also be prepared by the action of alcohols on acid chlorides
and anhydrides.
CH3CO Cl + H OC 2 H 5 -^CH 8 COOC 2 H 6 4- HCl
Acetyl chloride
CH3CO O COCH3 + H OC 2 H 5 -> CH3COOC8H5 + CH8COOH
Acetic anhydride
(4) By the action of alkyl halides on the silver salt of the acid.
CH3COO Ag + I C 2 H 5 -* CH 3 COOC 2 H 6 + AgI
This method is to be recommended when only a small quantity of the acid is
available, since both the conversion of the acid into its silver salt (p. 445) and of
the latter to the ester give almost quantitative yields.
(5) Esters of the binary halogen acids (HCl, etc.) can be prepared by the
PREPARATIONS 97
action of the corresponding phosphorus tri- or penta-halide. The reaction is
often indicated by the equation:
3C1H5OH + PCl8 = 3C 2 H 5 Cl + P(OH)8
Ethyl chloride Phosphorous acid
It is however more complicated, esters of phosphorous acid* being also formed
(cf. p. 308). Iodides are usually prepared by a modification of this method, the
cthanol being mixed with red phosphorus, and iodine added. The phosphorus
iodide is thus formed in situ, and at once reacts with ethanol to give the corres-
ponding iodide.
For reactions of esters, see p. 354.

Ethyl Acetate. CH3COOC2H5. (Method i.)


Required: Ethanol, 50 ml.; sulphuric acid, 10 ml.; acetic acid,
50 ml.; calcium chloride, 25 g.
Mix 50 ml. (40 g.) of ethanol and 50 ml. (52 g.) of glacial
acetic acid thoroughly in a 250 ml. round-bottomed flask, and
add slowly, with cooling and shaking, 10 ml. (18-5 g.) of con-
centrated sulphuric acid. Ensure that the liquid is homo-
geneous, then fit the flask with a reflux water-condenser (Fig. 8,
p. 17) and boil the mixture gently over a wire gauze for 10
minutes. Now alter the position of the condenser (Fig. 59, p. ioo,
or Fig. 23(0), p. 45) and distil off about two-thirds of the mixture
and then transfer the distillate to a separating-funnel.t Add about
25 ml. of 30% sodium carbonate solution, cork the funnel and
shake carefully in order to neutralise and remove the free acetic
and sulphurous acids present in the crude ethyl acetate: much
carbon dioxide is evolved during the shaking, therefore release
the pressure in the funnel at frequent intervals by cautiously
removing the cork, or alternatively by inverting the securely
corked funnel and momentarily opening the tap. Now allow the
two layers to separate, and carefully run off and reject the lower
aqueous layer, ensuring that the sodium carbonate solution is
removed as completely as possible. Then prepare a solution of
25 g. of anhydrous calcium chloride in 25 ml. of water, add it to
the ethyl acetate in the funnel, and again shake vigorously. The
calcium chloride solution removes any unchanged ethanol present
in the ethyl acetate. Allow the mixture to separate, and again run
off the lower aqueous layer as completely as possible. Then run
the ethyl acetate into a small conical flask, add a few lumps of

* See also Saunders et al.t J. Chem. Soc., 1945, 380.


t If a separating-funnel of only ioo ml. capacity is available, divide the dis-
tillate into two portions, and work up each separately as far as the drying stage.
98 PRACTICAL ORGANIC CHEMISTRY
granular calcium chloride, and shake occasionally.
After about 20 minutes, when the liquid should be dry, filter it
through a small fluted filter-paper into a ioo ml. distilling-flask
attached to a water-condenser. Add some fragments of unglazed
porcelain to the ethyl acetate, fit a 100° thermometer to the flask,
and place the latter on a cold water-bath, which is then brought
to the boil. Some ether is always formed as a by-product with the
ethyl acetate, and by these means is carefully distilled off as a
preliminary and separate fraction, boiling at 35-40°: if the dis-
tilling-flask is rapidly heated on a previously boiling water-bath,
however, the ether does not distil as a definite fraction, and the
boiling-point of the distillate steadily rises without a perceptible
break to that of the ethyl acetate itself. Collect the portion of the
distillate boiling between 74° and 79°, rejecting a small fraction
boiling immediately below this range. Yield 50 g. Ethyl acetate
is a colourless liquid having b.p. 77° and d, 0-92; it has a pleasant
apple-like odour, and is only slightly soluble in water.

Ethyl Acetate. (Semi-micro scale)


Required: Ethanol, 5 ml.; acetic acid, 5 ml.; sulphuric acid, i ml.;
calcium chloride, 2-5 g.
Use the apparatus shown in Fig. 38, p. 63, using a thermometer
reading to 100° and with water running through the vertical condenser.
Place in the 25 ml. pear-shaped flask 5 ml. of ethanol, 5 ml. of glacial
acetic acid and add carefully with shaking i ml. of concentrated sul-
phuric acid. Attach the flask to the reflux condenser and boil the
mixture gently for 10 minutes.
Now run the water out of the vertical condenser and pass water
through the inclined condenser. Continue to heat the mixture so that
everything distilling up to 82° is collected. Transfer the distillate to a
25 ml. separating funnel and add 3 ml. of 30% sodium carbonate
solution. Cork the funnel and shake carefully to remove acids, taking
all the precautions mentioned in the macro preparation above. Run
off and reject the lower layer. Dissolve 2-5 g. of anhydrous CaCl2 in
2-5 ml. of water, and add it to the ethyl acetate in the funnel and shake
vigorously. Again run off the lower layer and then add one or two
small pieces of granular CaCl2 to the liquid while still in the separating
funnel. Shake the liquid which will become clear in a few minutes.
Now decant the dried liquid into a small distilling flask of about
io ml. capacity (Fig. 36, p. 63). Distil the liquid and collect the
fraction b.p. 74-79°. Yield, 3 g.
Calculation of Yield. The yield of a compound obtained in an organic
preparation, in addition to being stated in grams, should also be calculated as a
percentage of the yield theoretically possible from the weight of the original
PREPARATIONS 99
compounds taken. Thus in the preparation of ethyl acetate, the equation
shows that 60 g. of acetic acid and 46 g. of ethanol react to give 88 g. of ethyl
CH3COOH + C 2 H 5 OH = CH 3 COOC 2 H 5 + H 2 O
60 46 88
acetate. If equimolecular quantities of acid and alcohol had been taken in
the preparation, the percentage yield of the ethyl acetate would clearly be
the same if calculated on the basis of either reagent. Actually, however, an
excess of ethanol was used and the yield can therefore be calculated on the basis
either of the ethanol or of the acid. Thus
46 g. of ethanol should give 88 g. of ethyl acetate
-'.4°g- »» M »» » 76 g. ,, M

Actually 50 g. of ester were obtained. Hence yield of ethyl acetate

= 5° X 10
° = 66o/0.
76
Similarly, since 60 g. of acetic acid should theoretically give 88 g. of
ethyl acetate, 52 g. should give 77 g. of the ester, and hence the yield,

calculated on the acetic acid, is = 65%.


77
(The yield of ester based on the ethanol taken is actually higher than the above
value, as the rectified spirit used contains only 96% of ethanol.)

Hydrolysis of Ethyl Acetate.


When esters such as ethyl acetate are shaken with water, hydrolysis slowly
occurs, and ultimately an equilibrium is attained:
CH 3 COOC 2 H 6 + HOH^ CH3COOH + C 2 H 6 OH
Complete hydrolysis can be rapidly obtained, however, if the ester is boiled
under reflux with a dilute aqueous solution of either a caustic alkali, such as
sodium hydroxide, or of a strong inorganic acid, such as sulphuric or hydro-
chloric acid. In the former case, the sodium hydroxide neutralises the acetic
acid as fast as it is formed, and so promotes the hydrolysis: in the latter case,
the dilute inorganic acid catalyses the hydrolysis, which in the presence of a
large excess of water goes practically to completion. Since the sodium salts
of some of the higher fatty acids are soaps, the general process of alkaline
hydrolysis of esters (by which the soaps are obtained) is frequently called
saponification.
Place 5 ml. of ethyl acetate in a ioo ml. round-bottomed flask, and
add about 50 ml. of io% sodium hydroxide solution, together with some
fragments of unglazed porcelain. Fit the flask with a reflux water-
condenser, and boil the mixture gently over a wire gauze for 30 minutes.
Now disconnect the condenser, and fit it by means of a bent delivery-
tube (or "knee-tube") to the flask for direct distillation (Fig. 59, or
Fig. 23(0), p. 45). Reheat the liquid, and collect the first 10 ml. of
distillate, which will consist of a dilute aqueous solution of ethanol.
Confirm the presence of ethanol by the iodoform test (Test 3, p. 336).
100 PRACTICAL ORGANIC CHEMISTRY

The residual liquid in the flask is a dilute alkaline solution of sodium


acetate. To liberate the acetic acid, add dilute sulphuric acid until
the solution is definitely acid to litmus, and then distil off about 20 ml.
Perform on this aqueous distillate the tests for acetic acid given on p.
347-
Hydrolysis of Ethyl Acetate (Semi-Micro Scale)
The hydrolysis of as little as 0-5 ml. of the ester can be carried out in the
combined "reflux-distillation" apparatus shown in Fig. 38 (p. 63). Pass a
stream of cold water through the vertical condenser. Place in the 10 ml. pear-
shaped flask 0-5 ml. of the ester, 5 ml. of 10% NaOH solution and one or two
minute fragments of unglazed porcelain and heat the mixture gently for 15
minutes so that the vapours do not rise more than about half-way up the vertical
water-condenser. Now run the water out of the vertical condenser, insert a
thermometer at the top, and pass water through the inclined condenser. Heat the
flask sufficiently strongly to collect 1-2 ml. of distillate. This is dilute ethanol.
Add dil. H 2 SO 4 to the residue in the flask until definitely acid to litmus.
Distil off 1-2 ml., and perform tests on this aqueous distillate for acetic acid.

Ethyl Bromide. C2H5Br. (Method i, p. 95.)


Ethyl bromide is an example of an ester formed from an alcohol and an
inorganic acid. Since hydrogen bromide is a gas, it is generated actually in
the reaction mixture, where it is rapidly esterified without appreciable loss.
For this purpose, a solution of ethyl hydrogen sulphate is prepared by adding
sulphuric acid to an excess of ethanol. Sodium bromide is then added, and the
liberated hydrogen bromide reacts with the ethyl hydrogen sulphate, giving
C,H6 HSO4 + H Br -^C 2 H 5 Br + H8SO4
ethyl bromide. The excess of ethanol ensures that the sulphuric acid liberated in
this reaction is reconverted into ethyl hydrogen sulphate, and that the excess of
the latter in turn effects maximum conversion of the costly hydrogen bromide
to ethyl bromide.
Required: Ethanol, 37 ml.; sulphuric acid, 40 ml.; sodium
bromide (NaBr^H 2 O), 35 g.
PREPARATIONS 101
Assemble the apparatus shown in Fig. 60. A is a 500 ml.
bolt-head flask connected by a "knee-tube" B to a water-
condenser C, to the lower end of which is fitted the adaptor D.
In view of the low boiling-point of the ethyl bromide, it is
essential that the various portions of the apparatus are connected
together by well-bored, tightly fitting corks. (For this reason, the
apparatus shown in Fig. 23(0), p. 45, is preferable.)
Arrange the adaptor D so that the end dips below the surface of
about 50 ml. of water contained in a small conical flask, or beaker,
which is in turn surrounded by a mixture of ice and water. Place
37 ml. (30 g.) of ethanol and 25 ml. of water in the flask A, and
then add slowly 40 ml. (74 g.) of concentrated sulphuric acid,
shaking the mixture gently around and cooling meanwhile. Now
a
^d 35 g. of coarsely powdered sodium bromide (2H 2 O),
reconnect the flask to the tube B without delay, and then heat
the flask gently on a sand-bath, at the same time ensuring that an
ample supply of cold water is passing through the condenser C.

FIG. 60.
Ethyl bromide soon distils over, and collects as heavy oily drops
under the water in the receiving flask, evaporation of the very
volatile distillate being thus prevented. If the mixture in the flask
A froths badly, moderate the heating of the sand-bath. When no
more oily drops of ethyl bromide come over, pour the contents of
the receiving flask into a separating-funnel, and carefully run
off the heavy lower layer of ethyl bromide. Discard the upper
aqueous layer, and return the ethyl bromide to the funnel. Add
an equal volume of 10% sodium carbonate solution, cork the
funnel securely and shake cautiously. Owing to the presence of
hydrobromic and sulphurous acids in the crude ethyl bromide, a
brisk evolution of carbon dioxide occurs: therefore release the
102 PRACTICAL ORGANIC CHEMISTRY
pressure in the funnel at frequent intervals (as in the preparation
of ethyl acetate, p. 97). Allow the two liquids to separate, and
again run off the lower layer of ethyl bromide. Discard the upper
layer, return the ethyl bromide to the funnel, and shake it with an
equal volume of water to remove traces of sodium carbonate.
Allow the two liquids to separate, and finally run the lower layer
of ethyl bromide carefully into a small conical flask: add a few
pieces of calcium chloride, securely cork the flask and then occa-
sionally shake the mixture gently, protecting the liquid as much as
possible from the heat of the hand. The liquid should become
quite clear (and therefore dry) in about 20 minutes.
Then filter the ethyl bromide through a small fluted filter-paper
directly into a 60 ml. distilling-flask. Fit the flask with a 100° ther-
mometer, and a water-condenser having as before an ample supply
of cold water: then arrange the condenser so that its lower end
enters the neck of a small dry weighed conical flask, supporting
the latter in line with the condenser, and chilling it externally
by a mixture of ice and water. Distil the ethyl bromide slowly
from a water-bath, and collect the fraction boiling between
35° and 40°. Average yield, 23 g. In view of the low boiling-
point of the ethyl bromide, it should be preserved in a sealed
glass specimen tube (see Fig. 21, p. 41).
Ethyl bromide is a colourless liquid, of b.p. 38° and d, 1-45,
insoluble in water: as prepared above, it always contains some
diethyl ether.
Hydrolysis of Ethyl Bromide. Add a few drops of pure freshly
distilled ethyl bromide to 2-3 ml. of aqueous silver nitrate solution in
a test-tube and shake. Only a faint opalescence of silver bromide
should be formed. Now carefully warm the mixture in a small Bunsen
flame, with gentle shaking: silver bromide soon appears as a white
suspension which rapidly increases in quantity and becomes a heavy
precipitate. The ethyl bromide is thus moderately stable in cold
water, but rapidly hydrolysed by hot water.
n-Butyl Bromide. C4H9Br. (Method i, p. 95.)
The preparation of rc-butyl bromide as an example of ester formation by
Method i (p. 95) has certain advantages over the above preparation of ethyl
bromide. w-Butanol is free from Excise restrictions, and the /i-butyl bromide is
of course less volatile and therefore more readily manipulated without loss than
ethyl bromide: furthermore, the w-butyl bromide boils ca. 40° below w-butyl
ether, and traces of the latter formed in the reaction can therefore be readily
eliminated by fractional distillation.
Required: Sodium bromide, 35 g.; w-butanol, 25 ml.
Place 30 ml. of water, 35 g. of powdered sodium bromide and
PREPARATIONS 103
25 ml. (20 g.) of fl-butanol in a 250 ml. round-bottomed flask, and
then fit a dropping-funnel to the flask through a cork which has a
groove cut or filed in the side (as F in Fig. I(B), p. 3) to allow escape of
air. Place 25 ml. of concentrated sulphuric acid in the funnel, and then
allow the acid to fall slowly dropwise into the flask, keeping the contents
well shaken meanwhile and cooled occasionally in an ice-water bath.
When the addition is complete, replace the funnel with a reflux water-
condenser, and then gently boil the mixture over a sand-bath for ca. 45
minutes, shaking the flask gently from time to time. Then remove the
reflux condenser, and fit a "knee-tube" and condenser to the flask
as shown in Fig. 59, p. ioo or Fig. 23(0), p. 45, and distil off the crude
n-buryl bromide (ca. 30 ml.). Purify the distillate by first shaking it with
water in a separating-funnei: run off the lower layer of bromide, reject
the aqueous layer, and then return the bromide to the funnel and shake
it with about half its volume of concentrated sulphuric acid; now run
off the lower layer of acid, and shake the bromide layer in the funnel
cautiously with dilute sodium carbonate solution, taking care to release
the pressure in the funnel at frequent intervals.
Run off the lower layer of bromide, dry it with calcium chloride (as
in the above preparation of ethyl bromide) and finally distil the filtered
bromide from a small flask, preferably through a short column. Collect
the w-butyl bromide as a colourless liquid of b.p. 99-102°. Yield, 30 g.
A small residue of di-w-butyl ether, b.p. 142°, remains in the flask.

The Alkyl Halides. Elhyl bromide and iodide (see below) are typical
alkyl halides. Compounds of this class are of very great importance in syn-
thetic work, owing to the reactivity of the halogen atom. This is illustrated
by the following general reactions:
(1) Reduction gives the corresponding hydrocarbon.
C 2 H 5 Br -f H 2 -> HBr -f- C 2 H 8 (ethane).
(2) Elimination of halogen by sodium (Wurtz's reaction) gives a higher
hydrocarbon.
C 2 H 5 Br -r 2Na -f BrC 2 H 3 -> 2NaBr -f C4H10 (normal butane).
(3) (a) Aqueous potassium hydroxide gives the alcohol.
C 2 H 5 Br + KOH ->KBr -f- C 2 H 6 OH (cthanol).
(b) Alcoholic potassium hydroxide gives an unsaturated hydrocarbon, often
however in only low yield with the earlier members of the series.
C 2 H 5 Br ; KOH ->H 2 O + KBr -f C 2 H 4 (ethylene).
(4) Sodium ethoxide gives an ether (Williamson's reaction).
C 2 H 5 Br -f NaOC 2 H 5 — NaBr + C 2 H 6 OC 2 H 6 (diethyl ether).
(5) (a) Potassium cyanide gives an alkyl cyanide or nitrile.
C 2 H 5 Br -f KCN -KBr -f C 2 H 6 CN (ethyl cyanide or propionitrile)
IQ4 PRACTICAL ORGANIC CHEMISTRY
(b) Silver cyanide gives an alkyl isocyanide or z'sonitrile.
C 2 H 5 Br - AgCX --- AgBr + C 2 H 5 NC (ethyl wocyanide).
(6) Silver nitrite gives a mixture of ethyl nitrite and nitro-ethane (p. 131).
C H Br AeXO S* C 2 H 5 -O-NO (ethyl nitrite)
2 5
' *' 2 \ C 8 H 5 NO 2 (nitro-ethane).
(7) Ammonia gives the corresponding amine (see however p. 127).
C 2 H 5 Br -r HNH 2 — HBr -r C 2 H 5 NH 2 (monoethylamine).
(8) The alkyl halides are also of great importance in synthetic operations (e.g.)
using Grigard reagents (p. 280), acetoacetic ester (p. 269) and malonic ester
(p. 275).
Ethyl Benzoate. C6H5COOC2H5. (Method 2; The Fischer-
Speier Method, p. 96.)
As a general rule esterification by the Fischer-Speier method should be
carried out using absolute ethanol: in the following preparation of ethyl benzoate,
however, the yield is not sensibly affected by the use of the cheaper rectified
spirit.
Required: Benzoic acid, 20 g.; rectified spirit, 20 ml.
Assemble in a fume-cupboard the apparatus shown in Fig. 61.
A is a wide-necked round-bottomed ioo ml. flask to which the
reflux water-condenser B is fitted by means of a rubber stopper.
The latter carries also an inlet tube C (which should not be too
narrow in diameter), by means of which a current of hydrogen
chloride, dried by passage through the sulphuric acid wash-bottle
D, can be passed down to the bottom of A. The hydrogen chloride
is best generated by means of a Kipp's apparatus charged with
solid ammonuim chloride and concentrated sulphuric acid. The
top of the condenser B is fitted with a calcium chloride tube* R,
preferably bent downwards as shown: drops of water tend to
collect in the end of E as hydrogen chloride steadily escapes during
the experiment, and are thus prevented from running back and so
fouling the calcium chloride. (Alternatively, the flask, condenser
and inlet-tube can be replaced by the apparatus shown in Fig.
23(B), p. 45-)
Place 20 g. of benzoic acid and 20 ml. (16 g.) of ethanol in A,
connect up the apparatus, and then heat the flask on a sand-bath
so that the solution in the flask boils gently. At the same time,
pass a brisk current of hydrogen chloride into the reaction
* In all experiments in which an apparatus is closed by means of a calcium
chloride tube, great care should be taken to ensure before the experiment that
there is a free air-passage through the tube. This applies particularly when the
tube has not been freshly charged, or in experiments where the heating has to
be stopped during the night and started again next day: in both cases an air-
tight crust of hydrated calcium chloride may have formed on the surface of the
anhydrous material. The small uniformly sized pellets of the calcium chloride
are best held in position by loose plugs of glass wool at each end of the tube.
PREPARATIONS
mixture. The speed with which the
hydrogen chloride enters the flask A
must be carefully watched during the
first few minutes of the experiment,
and any tendency of the solution to
suck back along the tube C (owing to
the high solubility of hydrogen
chloride in ethanol) should be checked
by increasing the current: when
once the boiling solution is saturated,
however, the current of hydrogen
chloride can be cut down until only
a gentle stream of bubbles is passing
through D.
When the solution has been boiling
for 11 hours, remove A, cool the
contents, and then pour the ethanolic
solution of the ester into a separating-
funnel containing about 200 ml. of
water, finally rinsing out the flask
with a few ml. of water which are also
doured into the funnel. Since the FIG. 61.
pensity of ethyl benzoate is only
slightly greater than that of water, a sharp separation of the ester
is not usually obtained. It is advisable at this stage therefore to
add about 10 ml. of carbon tetrachloride, and then to shake the
mixture in the funnel vigorously: on standing, the heavy solution
of the ethyl benzoate in the carbon tetrachloride separates sharply
and rapidly at the bottom of the funnel. Run off the ethyl
benzoate solution carefully, reject the upper aqueous layer, and
then return the ethyl benzoate to the flask and shake it with a
very dilute solution of sodium carbonate until all free acid is
removed and no further evolution of carbon dioxide occurs.
Run off the lower layer into a small conical flask, and dry by the
addition of a few pieces of granular calcium chloride. Cork the
flask and allow to stand for about 20 minutes with occasional
shaking. Then filter the ethyl benzoate solution through a small
fluted filter-paper directly into a 50 ml. distilling-flask containing
a few pieces of unglazed porcelain. Fit the flask with a 360°
thermometer and an air-condenser: in view of the small quantity
of carbon tetrachloride present, a water-condenser during the
early stages of the distillation is not necessary. By direct heating
over a gauze, distil first the carbon tetrachloride slowly, and then
106 PRACTICAL ORGANIC CHEMISTRY
the ethyl benzoate, collecting the latter as a fraction of b.p. 210-
214°. Yield, 19-20 g.
Ethyl benzoate is a colourless liquid, of b.p. 213° and d, 1-05;
almost insoluble in water: it has a characteristic odour.
For a further example of the Fischer-Speier method, see Ethyl cinnamate,
p. 235-
Ethyl Iodide. C2H6I. (Method 5, p. 96.)
This is a modification of Method 5, iodine being added to a mixture of red
phosphorus and ethanol: phosphorus tri-iodide is thus formed in situ, and
readily reacts with the ethanol, giving ethyl iodide and phosphorous acid (p. 96).
Required: Red phosphorus, 2-5 g.; ethanol, 25 ml.; iodine,
25 g;
Fit a 250 ml. round-bottomed flask securely by means of a
tightly fitting, well-bored cork to a reflux condenser capable of
talking an ample supply of water. Place in the flask 2-5 g. of red
phosphorus, and then 25 ml. (20 g.) of ethanol. Well powder
25 g. of iodine, and add it to the contents of the flask in small
quantities of about 3-4 g. at a time, allowing about two minutes
between consecutive additions: for this purpose, the flask should
be detached from the condenser immediately before each addition,
the iodine rapidly dropped into the flask and the latter at once
returned to the condenser. A moderate evolution of heat occurs,
but if the addition of the powdered iodine is carefully performed,
the contents of the flask should not actually boil. When all the
iodine has been added, allow the product to stand for 10 minutes,
and then heat on a boiling water-bath for i hour. Then change
the position of the condenser for direct distillation, attaching it
by means of a knee-tube to the flask, as shown in Fig. 59, p. ioo,
or Fig. 23(0), p. 45. Reheat the flask on a boiling water-bath, and
collect the distillate, which consists of ethyl iodide and unchanged
ethanol, usually coloured by traces of free iodine. When the dis-
tillation ceases, transfer the distillate to a separating-funnel, and
shake with an equal volume of 10% aqueous sodium carbonate
solution. Run off the lower layer of ethyl iodide, and discard the
upper aqueous layer. Return the ethyl iodide to the separating-
funnel, and shake it with an equal volume of water to remove
traces of sodium carbonate solution. Run off the lower layer of
ethyl iodide into a small conical flask, making the separation of the
iodide from the upper aqueous layer as sharp and complete as
possible. Add some pieces of granular calcium chloride, cork
the flask and allow to stand for 15-20 minutes, occasionally
shaking the contents gently. Then filter the ethyl iodide through
a small fluted filter-paper directly into a 60 ml. distilling-flask.
PREPARATIONS 107
Fit the flask with a 100° thermometer and a water-condenser, and
distil the ethyl iodide carefully from a water-bath, collecting the
fraction which distils between 68° and 73°. Yield, about 24 g.
Ethyl iodide is a heavy liquid, of b.p. 72° and of d, 1-94; in-
soluble in water. When freshly distilled it is colourless, but on
prolonged exposure to light it darkens in colour owing to the
liberation of free iodine. Its chemical properties are almost
identical with those of ethyl bromide given on pp. 102 and 103.
Acetylation.
Compounds of the type ROH (alcohols and phenols), and also compounds
of the type RNH 2 and R 2 NH (primary and secondary amines) can be directly
acetylated, the reactive H atom being replaced by the acetyl radical,
-COCH3. The acetylation of alcohols and phenols is really a special case of
esterification, since the acetyl derivative, ROCOCH3, is clearly an ester
of acetic acid. Primary and secondary amines similarly give acetyl derivatives
of the type RNHCOCH 3 and R 2 NCOCH 8 respectively, which can be regarded
as mono-and di-substituted derivatives of acetamide, H 2 NCOCH 3 .
The two chief methods of acetylation are:
(1) Heating with a mixture of acetic anhydride and acetic acid.
If a primary or secondary amine is heated with glacial acetic acid, the
RNH H + HOOCCH 3 -> NHCOCH 3 -f H 2 O
corresponding acetyl derivative is produced, but the process is often extremely
slow. If, however, the acetic acid is mixed with acetic anhydride, rapid
acetylation usually results.
RNHH -f CH 3 CO-O- COCH 3 ->RNHCOCH 3 -f CH3COOH
One disadvantage of using acetic anhydride is that with primary amines,
traces of the diacetyl compound, RN(COCH 3 ) 2 , may be formed: the chances of
this secondary acetylation are, however, usually remote, and recrystallisation
from an aqueous solvent will generally hydrolyse the diacetyl derivative rapidly
back to the mono-acetyl compound.
For complete acetylation of polyhydric compounds, such as glucose (p. 141)
and mannitol (p. 142), even undiluted acetic anhydride is insufficient, and a
catalyst must also be employed. In such cases, the addition of zinc chloride
or anhydrous sodium acetate to the acetic anhydride usually induces complete
acetylation.*
(2) Treatment with acetyl chloride.
Acetylation will proceed particularly smoothly with acetyl chloride if pyridine
is present to absorb the hydrogen chloride as fast as it is formed.
RO H -f Cl COCH3 ->ROCOCH3 -f HCl
Acetylation has two chief uses: (i) to characterise and identify hydroxy
* Some amines, e.g., aniline, can on the other hand be readily acetylated by
dissolving them in cold dil. acetic acid and adding acetic anhydride: the method
is not however general.
io8 PRACTICAL ORGANIC CHEMISTRY
compounds and primary and secondary amines, by obtaining crystalline acetyl
derivatives. This applies particularly to aromatic compounds, since aliphatic
compounds are often liquid, and frequently soluble in water; (2) to protect a
primary or secondary amino group during a chemical reaction, as in the pre-
paration of />-nitro-aniline by the nitration of acetanilide, followed by hydrolysis
(p. 167), and in the preparation of sulphanilamide (p. 181).

Acetanilide. C6H5NHCOCH3. (Method i.)


Required: Acetic acid/anhydride mixture, 20 ml.; aniline,
io ml.
Add 20 ml. of a mixture of equal volumes of acetic anhydride
and glacial acetic acid to io ml. (10-3 g.) of aniline contained
in a 150 ml. conical flask. Fit a reflux water-condenser to the
flask, and boil the mixture gently for io minutes. Then pour
the hot liquid into 200 ml. of cold water, stirring the latter well
C 6 H 6 NH 2 + O(OCCH 3 ) 2 = C 6 H 5 NHCOCH 3 + CH3COOH
during the addition. The acetanilide rapidly crystallises. Filter
at the pump, and wash the crude acetanilide well with water.
Recrystallise from about 60 ml. of a mixture of one volume of
acetic acid and two volumes of water: filter off the colourless
crystals at the pump, again wash thoroughly with water, drain,
and dry. M.p. 113°; yield, io g. Alternatively, the crude
acetanilide may be recrystallised from boiling water, but in this
case a much greater volume (about 300 ml.) of the solvent will be
required.
Acetanilide (Semi-micro Scale) (1/40 of above scale).
Run into a test-tube from a micro-burette 0-25 ml. of aniline and
0-5 ml. of the 1:1 acetic acid-acetic anhydride mixture. Insert a
"cold finger" (Fig. 35, p. 62) into the lip of the test-tube, without using
a cork. Circulate the water through the finger and gently boil the mix-
ture for 5 minutes. Cool, add about 5 ml. of cold water, stir well with
a thin glass rod and filter off the precipitated acetanilide using the
apparatus shown in Figs. 45 or 46 (p. 68). Use the filtrate to effect the
complete transfer of all the solid from the test-tube to the filter funnel,
and then wash the solid with about i ml. of ice-cold water and drain
thoroughly. Recrystallise from boiling water (about 8 ml.). Filter if
necessary while hot through a very small fluted filter paper (or using
the apparatus shown in Fig. 47, p. 68) into a small conical flask or test-
tube. When quite cold filter off the purified acetanilide, again using
the apparatus shown in Figs. 45 or 46. Yield, 0-2 g.
Hydrolysis of Acetanilide. Anilides in general, such as acetanilide
and benzanilide (p. 245), may be hydrolysed by caustic alkalis or by
acids. Alkaline hydrolysis, however, is usually very slow, and therefore
PREPARATIONS 109
acid hydrolysis should always be used for anilides. For this purpose, a
70% solution of sulphuric acid, prepared by adding 40 ml. (74 g.)
of the concentrated acid cautiously to 30 ml. of water with cooling
and stirring, gives the most satisfactory results.
Place i g. of acetanilide and 10 ml. of the 70% sulphuric acid in a
small flask fitted with a reflux water-con denser, and boil the mixture
gently for 15 minutes, when the hot solution will smell perceptibly of
free acetic acid. Dilute the solution with about 5 ml. of water,
C 5 H 6 NHCOCH 3 +H 2 O + H2SO4 = C 6 H 5 NH 21 H 2 SO 4 + CH3COOH
transfer it to a small distilling-flask, and distil off about 1-2 ml. Acetic
acid is volatile in steam: therefore apply to this distillate the tests for
free acetic acid given on p. 347. Cool the residual liquid, which
contains aniline sulphate dissolved in excess of dilute sulphuric acid,
and apply the tests for aniline given on p. 373.
Alternatively the semi-micro apparatus shown in Fig. 38 (p. 63) may be used.
Heat the anilide and sulphuric acid under reflux for 15 minutes in such a
manner that the vapour does not rise higher than half-way up the vertical
condenser through which water is passed. Then dilute the solution in the flask
with 5 ml. of water. Empty the vertical condenser and run cold water through
the inclined condenser. Now increase the rate of heating and distil off 1-2 ml.
of aqueous acetic acid.

Phenyl Acetate. CH3COOC6H6. (Method i modified.)


Although the acetylation of alcohols and amines by acetic anhydride is
almost invariably carried out under anhydrous conditions owing to the ready
hydrolysis of the anhydride, it has been shown by Chattaway (1931) that
phenols, when dissolved in aqueous sodium hydroxide solution and shaken with
acetic anhydride, undergo rapid and almost quantitative acetylation if ice is
present to keep the temperature low throughout the reaction. The success of
this method is due primarily to the acidic nature of the phenols, which enables
them to form soluble sodium derivatives, capable of reacting with the acetic
CH3CO-O-COCH3 + NaOC 6 H 5 -> CH3COOC6H5 + CH3COONa
anhydride before the latter undergoes appreciable hydrolysis. The general
conditions of the acetylation are thus similar to those used in the Schotten-
Baumann method for benzoylation (p. 243).
When the phenol contains a carboxylic acid group, e.g., m- or p-hydroxy-
benzoic acid, the acetylated derivative will of course remain in solution as the
sodium salt, but is precipitated when the solution is subsequently acidified.
Salicylic acid, however, cannot be acetylated under these conditions.
Some amino-acids, e.g., glycine, can also be acetylated by this method.
Required: Phenol, 15 g.; acetic anhydride, 22 ml.
Dissolve 15 g. of phenol in 105 ml. (1.6 mols.) of 10% aqueous
sodium hydroxide solution contained in a stout-walled bottle, and add
about 150 g. of crushed ice. Then add 22 ml. (24 g., 1.5 mols.) of acetic
i io PRACTICAL ORGANIC CHEMISTRY
anhydride, cork the bottle securely, and shake the contents vigorously
for about 5 minutes, by which time the reaction will be complete and
an emulsion of phenyl acetate obtained.
Pour the mixture into a separating-funnel. Owing to the density of
the acetate being only slightly greater than that of water, a sharp
separation is usually not rapidly obtained. It is advisable therefore to
add about 8 ml. of carbon tetrachloride, when, after shaking, a sharp
and rapid separation of the heavy solution of the phenyl acetate in the
tetrachloride is obtained. Run off this solution, reject the upper
aqueous layer, return the solution to the funnel, and shake again with
about 8o ml. of very dilute sodium carbonate solution in order to
remove traces of acetic acid or anhydride. Run off the lower layer into
a small conical flask, dry over granular calcium chloride for 20-30
minutes and then filter through a small fluted filter-paper directly into
a 50 ml. distilling-flask. Fit the latter with a 360° thermometer and an
air-condenser and distil the contents slowly by heating over a gauze.
(The quantity of carbon tetrachloride present is too small to make the
preliminary use of a water-condenser necessary.) The boiling-point of
the mixture rises slowly but steadily to about 170° before the distillation
of the carbon tetrachloride is complete, and then rises rapidly to about
193°. Collect the phenyl acetate as the fraction of b.p. 193-197°.
Yield, 20 g.
Phenyl acetate is a colourless liquid, of b.p. 196° and dy ro8, almost
insoluble in water and almost odourless.

2-Naphthyl Acetate. CH3COOC10H7. Dissolve i g. of pure


2-naphthol in 5 ml. (1-8 mols.) of io% sodium hydroxide solution as
before, add io g. of crushed ice, and ri ml. (1*14 g., 1-5 mols.) of
acetic anhydride. Shake the mixture vigorously for about 10-15
minutes; the 2-naphthyl acetate separates as colourless crystals. Filter
at the pump, wash with water, drain, and dry thoroughly. Yield of
crude material, 1-4 g. (theoretical). Recrystallise from petroleum
(b.p. 6o-8o°), from which, on cooling and scratching, the 2-naphthyl
acetate separates as colourless crystals, m.p. 71°: yield, ro g.
8
Acetylsalicylic Acid (Aspirin). C 6 H X (Method2)
Required: Salicylic acid, io g.; pyridine, 7 ml.; acetyl chloride,
ml
TS -
Dissolve io g. of salicylic acid (o-hydroxybenzoic acid) in
7 ml. of dry pyridine contained in a ioo ml. conical flask. Then
without delay (since this solution if allowed to stand tends to
become a semi-solid mass) run in 7-5 ml. (8-3 g.) of acetyl
chloride, adding about i ml. of the chloride at a time, and shaking
the mixture continuously during the addition. The heat of the
reaction causes the temperature of the mixture to rise rapidly:
PREPARATIONS in
therefore maintain the latter between 50° and 60° throughout the
addition, cooling the flask occasionally in cold water if necessary.
Finally heat the mixture on a boiling water-bath for 5 minutes,
CH3COCl + HOC 6 H 4 COOH - CH 3 COOC 6 H 4 COOH + HCl
Salicylic Acid Aspirin
and then, after cooling in cold water, pour it in a thin stream into
about 300 ml. of cold water, stirring the mixture vigorously
meanwhile. The crude acetylsalicylic acid either solidifies at
once, or separates as an oil which rapidly crystallises as the
stirring proceeds. Filter the solid product at the pump, wash
thoroughly with water and drain. Recrystallise from a mixture
of equal volumes of water and acetic acid: yield, n g. (Alter-
natively, press the crude product between several sheets of drying-
paper until quite dry, and then recrystallise from benzene: a
sticky product will result, however, if traces of water still remain.)
The acetylsalicylic acid is obtained as colourless crystals, m.p.
136-137°.
It should be emphasised that salicylic acid can be readily acetylated by
Method i, and that the above preparation of acetylsalicyclic acid is given
solely as an illustration of Method 2. To employ Method i, add 10 g. of
salicylic acid to 20 ml. of a mixture of equal volumes of acetic anhydride and
acetic acid, and boil gently under reflux for 30 minutes. Then pour into about
200 ml. of cold water in order to precipitate the acetylsalicylic acid (n g.)
and finally recrystallise as above. Method 2, however, gives the purer product.
Acetylsalicylic acid is largely used in medicine as an analgesic
(i.e., for removing pain) and as an antipyretic (i.e., for reducing
the body temperature).
Reactions of Aspirin, (i) Distinction from Salicylic acid. Shake
up with water in two clean test-tubes a few crystals of (a) salicylic acid,
(b) aspirin, a very dilute aqueous solution of each substance being thus
obtained. Note that the addition of i drop of ferric chloride solution
to (a) gives an immediate purple coloration, due to the free —OH group,
whereas (b) gives no coloration if the aspirin is pure.
(2) Hydrolysis of Aspirin. Gently boil a mixture of i g. of
aspirin and 15 ml. of 10% sodium hydroxide solution in a 50 ml.
conical flask under reflux for 20 minutes. Then cool the solution
thoroughly and add dilute sulphuric acid until the precipitation of the
CH3COOC6H4COOH + 2NaOH = CH8COONa + HOC8H4COONa + H 2 O
salicylic acid is complete. Filter off the salicylic acid, recrystallise it
from hot water, and confirm its identity by reaction (i) above. M.p.
1 60
SThe
- original filtrate still contains the acetic acid which is the other
product of the hydrolysis. Therefore place this filtrate (which must be
ii2 PRACTICAL ORGANIC CHEMISTRY
distinctly acid to litmus-paper) in a distilling-flask and distil off about
5 ml. through a water-condenser. Then apply to the filtrate the tests
for acetic acid given on p. 347.
Oxalic Acid. COOH
9 2O2O.
COOH
Certain aliphatic compounds are oxidised by concentrated nitric acid, the
carbon atoms being split off in pairs, with the formation of oxalic acid. This
disruptive oxidation is shown by many carbohydrates, e.g., cane sugar, where
the chains of secondary alcohol groups, -CH(OH)-CH(OH)-CH(OH)-CH(OH)-,
present in the molecule break down particularly readily to give oxalic acid.
It should be noted that aliphatic compounds (except the paraffins) are usually
oxidised by concentrated nitric acid, whereas aromatic compounds (including
the hydrocarbons) are usually nitrated by the concentrated acid (in the presence
of sulphuric acid) and oxidised by the dilute acid. As an example of the latter,
benzaldehyde, C 6 H 6 CHO, when treated with concentrated nitric acid gives
m-nitrobenzaldehyde, NO 2 C 6 H 4 CHO, but with dilute nitric acid gives benzoic
acid, C6H6COOH.
Required: Cane sugar, 20 g.; nitric acid, ioo ml.
Owing to the copious evolution of nitrous fumes, this prepara-
tion must be carried out in a fume-cupboard having an efficient
draught. Place 20 g. of coarsely powdered cane sugar (sucrose)
in a 750 ml. flat-bottomed flask, add ioo ml. of concentrated
nitric acid and heat the flask on a boiling water-bath. As the
mixture becomes warm, the greater part of the sugar dissolves
and a vigorous but harmless reaction, accompanied by a tremen-
dous evolution of nitrous fumes, takes place. Immediately the
evolution of gas starts, remove the flask from the water-bath and
place it on a wooden block or some similar non-conducting
surface. When the reaction subsides (after about 15 minutes)
pour the hot solution into an evaporating-basin, wash out the flask
with about 20 ml. of concentrated nitric acid, and then evaporate
the acid solution on the water-bath until it has a volume of about
20 ml. Some oxidation continues in the solution during the
evaporation, which is comparatively rapid. Now add about 40 ml.
of water to the solution, and again evaporate to about 20 ml.
Cool the solution thoroughly in ice-water; oxalic acid rapidly
crystallises. When crystallisation is complete, filter at the pump,
and then recrystallise from a small quantity of hot water. Dry
by pressing between pads of drying-paper, or in an atmospheric
desiccator, but not in an oven where partial loss of water of
crystallisation may occur. Yield, 7 g. The hydrated acid
has m.p. 101°; the anhydrous acid decomposes on heating.
Oxalic acid is poisonous.
For reactions of oxalic acid, see p. 351.
PREPARATIONS 113
Formic Acid, HCOOH (in aqueous solution), and Lead
Formate, (HCOO)2Pb.
When a mixture of anhydrous glycerol and crystalline oxalic acid,
(COOH) 2 ,2H 2 O, is heated the glycerol undergoes esterification, giving first
glyceryl monoxalate (A): the latter, however, decomposes as the temperature
CH 3 (OH)-CH(OH)-CH 2 (OH) + (COOK) 2
-» H 2 O + CH 2 (OH)-CH(OH)-CH 2 O-CO COOH (A)
CH 2 (OH)-CH(OH)-CH 2 -OCO-COOH
-> CO 2 + CH 2 (OH)-CH(OH)-CH 2 O-CO-H (B)
CH 2 (OH) CH(OH)-CH 2 O-CO-H + H 2 O
-^CH 2 (OH)CH(OH)-CH 2 (OH) + HCOOH
reaches about 100°, losing carbon dioxide and giving glyceryl monoformate
(B). On further heating, particularly if more oxalic acid is added, the mono-
formate is hydrolysed (the necessary water being provided both by the oxalic
acid and by the first reaction), and consequently a distillate of aqueous formic
acid is obtained.
Required: Glycerol, 70 ml.; oxalic acid, 40 g.; lead carbonate.
Since glycerol is a very hygroscopic substance, it may be
necessary to ensure that the sample used is anhydrous. For this
purpose, place about 70 ml. in a porcelain evaporating-basin, and
heat it carefully over a gauze (preferably in a fume-cupboard),
stirring it steadily with a thermometer until the temperature is
175-180°: then maintain this temperature for a further 5 minutes.
Allow the glycerol to cool, but while it is still warm (i.e., before it
becomes viscous) pour 50 ml. (63 g.) into a 250 ml. distilling-
flask containing 40 g. of powdered crystalline oxalic acid. Fit
a thermometer in the flask so that the bulb is completely immersed
in the glycerol mixture, and then fit a water-condenser to the flask.
Heat the mixture carefully over a gauze so that the temperature
rises to 110-120°, and then adjust the heating so that the tempera-
ture remains within these limits. A vigorous effervescence of
carbon dioxide occurs, and the aqueous formic acid begins slowly
to distil over. When the effervescence tends to subside, remove
the Bunsen flame and allow the temperature to fall to 70-80°:
then add a further 40 g. of powdered oxalic acid, and continue
the heating as before. Ultimately 25-30 ml. of distillate are
obtained, the total period of heating being about i hour. While
the distillation is proceeding, withdraw a few ml. of the distillate
and apply Tests 2, 3 and 4 for formic acid given on p. 350—351.
To obtain lead formate, add about ioo ml. of water to the
distillate and then stir powdered lead carbonate into the gently
heated solution until no further effervescence of carbon dioxide
occurs. Then boil the mixture vigorously and filter at the pump,
H4 PRACTICAL ORGANIC CHEMISTRY
using a Buchner funnel. Evaporate the clear filtrate by direct
boiling in a beaker until crystals appear on the surface, and then
allow to cool, finally chilling in ice-water. The lead formate
separates as colourless crystals; filter off, wash with a small quan-
tity of cold water, and dry. Yield, about 6 g.
A considerable amount of the formic acid, however, still
remains behind in the distilling-flask as the unhydrolysed mono-
formate. Therefore, if time allows, dilute the residue in the flask
with about an equal volume of water, and then steam-distil, the
monoformate ester being thus completely hydrolysed and the
formic acid then driven over in the steam. Collect about 400 ml.
of distillate. Add this distillate to that obtained by direct
heating of the reaction mixture and then treat with lead carbonate
as described above. Total yield of lead formate is now about 40 g.

Lead formate is only slightly soluble in cold water, and insoluble in


hot absolute ethanol: it can therefore be readily distinguished from
lead acetate or "sugar of lead" because, quite apart from chemical
tests, the acetate is readily soluble in cold water and moderately soluble
in ethanol.
Lead formate separates from aqueous solution without water of
crystallisation. It can therefore be used for the preparation of an-
hydrous formic acid. For this purpose, the powdered lead formate
is placed in the inner tube of an ordinary jacketed condenser, and there
held loosely in position by plugs of glass-wool. The condenser is then
clamped in an oblique position and the lower end fitted into a receiver
closed with a calcium chloride tube. A current of dry hydrogen
sulphide is passed down the inner tube of the condenser, whilst steam
is passed through the jacket. The formic acid which is liberated
(HCOO)2Pb + H2S -» 2HCOOH + PbS.
collects in the receiver, and is then purified from dissolved hydrogen
sulphide by redistillation over a further quantity of lead formate.
For reactions of formic acid and formates, see p. 350-351.
If the reaction mixture used in the above preparation of formic acid is
heated to 190-200°, the glyceryl monoformate which has escaped hydrolysis
undergoes decomposition, with the loss of carbon dioxide and water, and the
CH2(OH)-CH(OH)-CH2O-CO-H -> CH2:CH-CH,OH + CO, + H 2 O
formation of allyl alcohol.
The neutral glyceryl oxalate (C), which is also formed in the reaction
CH8OH-CH CH mixture, loses carbon dioxide at the higher
i I temperature and thus also gives allyl alcohol.
O-C-C-O
Il Il
O O
PREPARATIONS 115
Potassium Antimonyl Tartrate (Tartar Emetic).
C4H4O6KSbO, ^H2O.
Tartaric acid is noteworthy for (a) the excellent way in which the majority
of its salts crystallise, and (6) the frequent occurrence of salts having mixed
cations. Examples of the latter are sodium potassium tartrate (or Rochelle
salt), C 4 H 4 O 6 NaK, used for the preparation of Fehling's solution (p. 525),
godium ammonium tartrate, C 4 H 4 O 8 NaNH 4 , used by Pasteur for his early
optical resolution experiments, and potassium antimonyl tartrate (or Tartar
Emetic), C 4 H 4 O 6 K(SbO). The latter is prepared by boiling a solution of
potassium hydrogen tartrate (or "cream of tartar") with antimony trioxide,
CH(OH)-COOK CH(OH)-COOK
2 I + Sb2O, -* 2 I 4- H 2 O
CH(OH)-COOH CH(OH)-COO(SbO)
when the acidic hydrogen atom is replaced by the monovalent antimonyl
(Sb:O) radical.*
Required: Potassium hydrogen tartrate, 5 g.; antimony trioxide,
Sg-
Add 5 g. of potassium hydrogen tartrate and 5 g. of antimony
trioxide (each being finely powdered) to 30 ml. of water contained
in a small flask, and boil the mixture under a reflux water-
condenser for 15 minutes. Then filter hot, using a Buchner
funnel and flask which have been preheated by the filtration of
some boiling distilled water. Pour the clear filtrate into a beaker
and allow to cool. Potassium antimonyl tartrate separates as
colourless crystals. Filter, drain and dry. Yield, 5 g. The pro-
duct can be recrystallised from hot water, but this is usually not
necessary.
Tartar emetic, as its name indicates, can be used medicinally to cause vomiting.
For the preparation of tartar emetic intended for medicinal use, pure antimony
trioxide, free (in particular) from traces of arsenic, must of course be employed.

Acetic Anhydride. CH3CO O COCH3


Although some dibasic acids, e.g., succinic acid and phthalic acid, readily
lose water on heating with the formation of cyclic anhydrides, most monobasic
CH2COOH CH2CO
Heat j \O + H 2 O
CH2COOH * CH,CO
Succinic acid. Succinic anhydride.
carboxylic acids when heated merely distil unchanged. Their anhydrides can
however be prepared by the interaction of the acid chloride with a metallic salt of
* This is a simplified formula for tartar emetic, for X-ray crystal analysis and
infrared studies indicate that the Sb is a part of the antimonate anion [Sb(OH) 4 ]"
and forms part of a cyclic system.
ii6 PRACTICAL ORGANIC CHEMISTRY
the acid itself. Thus acetyl chloride and sodium acetate readily interact with
CH3CO Cl 4- Na GOCCH8 -^CH 3 CO-O COCH 3 + NaCl
the formation of acetic anhydride.
It should be emphasised that whereas the interaction of a sodium salt and an
acid chloride is a convenient general laboratory method for preparing all classes
of anhydrides, acetic anhydride is prepared on a large scale by other and cheaper
methods. Industrial processes are based on reactions indicated by the equations:
(1) CH3COONa + S + 6Clt -> 4(CH3CO)8O -f 6NaCl + Na1SO4
(2) CH.: C : O + CH3COOH -> (CH3CO)1O
ketene
Required: Anhydrous sodium acetate, 21 g.; acetyl chloride,
15 ml.
Place 2i g. (a 20% excess) of powdered anhydrous sodium
acetate* in a ioo ml. round-bottomed flask fitted with a reflux
water-condenser, and cool the flask in ice-water. Place 15 ml.
(16-5 g.) of acetyl chloride in a dropping-funnel fitted into the
top of the condenser by means of a grooved cork (c/. Fig. 53,
p. 76, or Fig. 23(A), p. 45). Now allow the acetyl chloride to run
slowly down into the chilled sodium acetate, thoroughly mixing
the contents by shaking as soon as the product becomes suffici-
ently liquid. Then heat the flask on a boiling water-bath for io
minutes to complete the reaction. Next disconnect the condenser
and fit it by means of a "knee-tube" Fig. 59, p. ioo, or Fig. 23(0),
p. 45) to the flask for distillation. Heat the flask with a luminous
smoky Bunsen flame (without a gauze), waving the flame around
the base of the flask to ensure uniform heating and to minimise
risk of cracking: continue heating until no more distillate passes
over. Now fractionally distil the crude acetic anhydride slowly
from a 40 ml. distilling-flask, preferably using an air-condenser.
A small quantity passes over at 130-135° (due to traces of free
acetic acid) and the major fraction at 135-140°. Yield, 18 g.
Add a few drops of the distillate to an aqueous silver nitrate solution con-
taining some dilute nitric acid and warm gently: no silver chloride should be
precipitated, indicating the complete absence of unchanged acetyl chloride.
Acetic anhydride is a colourless liquid, having b.p. 138° and
* For this preparation, it is particularly necessary that the sodium acetate
should be free from traces of water. The anhydrous material can be prepared
by gently heating the hydratcd salt (CH 3 COONa,3H 2 O) in an evaporating-
basin over a small Bunsen flame. The salt dissolves in its water of crystallisation
and resolidifies as this water is driven off: further heating then causes the an-
hydrous material to melt. Stir the molten anhydrous material to avoid charring,
and then allow it to cool in a desiccator. Powder the cold material rapidly in a
mortar, and bottle without delay.
If a sample of the anhydrous salt is taken from stock, it should preferably be
melted, allowed to cool, and then pulverised.
PREPARATIONS 117
d, i-08: it has a sharp pungent odour resembling that of acetic
acid. It is used in organic chemistry chiefly as an acetylating
agent, for which purpose it is frequently mixed with acetic acid,
sodium acetate, etc.: for examples of such acetylations see pp.
107-112.
For reactions of acetic anhydride, see p. 364.

Acid Amides.
Acid amides may be prepared by the following methods:
(1) Dehydration of the corresponding ammonium salt. Thus ammonium
acetate on heating loses water giving acetamide. An excess of acetic acid is
CH3COONH4 = CH1CONH1 + H t O
usually added before heating, in order to suppress thermal dissociation of the
ammonium acetate into ammonia and acetic acid.
(2) By the action of Concentrated Aqueous Ammonia on:
(a) Esters COOC 8 H 5 HNH, CONH 8
I + _> I + 2C2H6OH
CO OC8H5 H NH, CONH 2
Ethyl oxalate Oxamide
(b) Add Chlorides C6H5CO Cl + H NH 2 -> C.H^CONH, + HCl
Benzoyl Chloride Benzamide
(c) Acid Anhydrides
CH3CO O-OCCH, + H NH 2 -> CH 8 CONH 2 + CH8COOH
Acetic anhydride Acetamide
In reactions (b) and (c} the hydrochloric and acetic acids formed are of course
at once neutralised by the excess of ammonia.
Method (i) is most frequently used for aliphatic acid amides, while Methods
(2a), (26) and (2c) are used most frequently for aromatic acid amides. Of the
last three methods, the Acid Chloride Method (26) is the most rapid and
certain. The Ester Method (-20) is practicable only when the amide is insoluble
in water, and even then is often very slow unless the ester itself is appreciably
soluble in the aqueous ammonia solution.
For reactions of acid amides, see p. 560.

Acetamide. CH3CONH2. (Method i.)


Required: Ammonium carbonate, 15 g.; acetic acid, 50 ml.
Add 15 g. of finely powdered ammonium carbonate gradu-
ally to 50 ml. of glacial acetic acid contained in a 150 ml. round-
bottomed flask, shaking the mixture during the addition to ensure
a steady evolution of carbon dioxide. When all the carbonate has
n8 PRACTICAL ORGANIC CHEMISTRY
dissolved and the evolution of carbon dioxide has ceased, fit a
reflux air-condenser to the flask and boil the solution gently for
30 minutes, when the dehydration of the ammonium acetate will
be complete. Now remove the condenser and fit a fractionating
column to the flask: for this purpose a 4-pear column may be
used, but far better results are obtained if a column of the type
shown in Fig. U(B) (p. 26), in which the glass sections them-
selves occupy a height of about 12 cm., is used. Fit a 360°
thermometer in the column, and fit the air-condenser to the side-
arm for distillation. Now distil the liquid through the column
very slowly (to give about i drop of distillate every 3 seconds)
until the temperature reaches 170°: it is very important that this
operation should be carried out slowly in order to distil over as
much water and excess of acetic acid as possible, and so to leave
almost pure acetamide in the flask. Without delay, pour the hot
molten acetamide into a small (50 ml.) distilling-flask, and attach
the side-arm of the flask to a short glass tube (about 30 cms. long
and 12 mm. internal diameter) to act as an air-condenser. Distil the
acetamide carefully at such a rate that none escapes condensation,
and that none crystallises while still in the condenser. Collect
the fraction boiling between 215° and 225° directly into a weighed
specimen-tube, where it should crystallise readily on cooling.
Yield, 15 g.
Acetamide is thus obtained as a colourless crystalline solid,
which has a characteristic odour of mice, stated to be due to the
presence of small quantities of methylacetamide, CH 3 CONHCH 3 .
The acetamide can be purified and rendered odourless by re-
crystallisation from acetone, and then has m.p. 82°, b.p. 223°. If
this recrystallisation is contemplated, the distilled material should
be collected directly into a small weighed beaker or conical flask,
so that the solidified acetamide can be readily broken up and
removed.
Oxamide. NH2CO CONH2. (Method 2(a), p. 117.)
Required: Concentrated ammonia, 5 ml.; ethyl oxalate, i ml.
Oxamide differs from most aliphatic acid amides in being almost
insoluble in water,* and therefore can be readily prepared from the
diethyl ester by Method 2(a). Place a mixture of 5 ml. of concentrated
(d, o-88o) ammonia solution and 5 ml. of water in a 25 ml. conical
flask, for which a well-fitting cork is available. (The large excess of
* The very low solubility of oxamide is almost undoubtedly the result of the
extensively hydrogen-bonded nature of the crystalline compound (cf. E. M.
Ayerst and J / R . C. Duke, Acta. Cryst. (1954), 7, 588).
PREPARATIONS 119
ammonia solution is employed chiefly to prevent too great a rise in
temperature during the reaction.) Now add i ml. (i-i g.)of ethyl
oxalate, cork the flask securely and shake vigorously: the mixture
becomes perceptibly warm, and therefore throughout the shaking hold
the cork tightly in position, with the flask pointing away from the
operator (and from neighbouring students!). At intervals, release the
pressure by cautiously removing the cork. The oxamide rapidly separ-
ates as a white powder and after 15 minutes' shaking the reaction is
complete. Filter off the oxamide at the pump, wash it well with water
and drain thoroughly. Dry by pressing between sheets of drying-
paper, or in a desiccator. Yield 0-5 g. The low solubility of oxamide
in most liquids makes recrystallisation very difficult: the product
obtained in this preparation when dried is pure, however, and recrystal-
lisation is therefore not necessary. Oxamide has no definite melting-
point, as on heating it partly sublime* and partly decomposes.
Succinamide. NH2COCH2-CH2CONH2. (Method z(a)). Add
5 ml. (5-8 g.) of dimethyl succinate to a mixture of 50 ml. of water
and 25 ml. of concentrated (d, o-88o) aqueous ammonia solution in a
150 ml. conical flask. Cork the flask and shake the contents: the
dimethyl succinate rapidly dissolves to give a clear solution. Allow the
solution to stand; after about i hour the succinamide starts to crystal-
lise, and then continues to separate for some time. Next day, filter off
the succinamide at the pump, wash with cold water, and drain. Re-
crystallise from water, from which the succinamide separates as
colourless crystals: the latter soften at 240° and melt at 254-255° with
CH 2 CONH 2 CH2CO
= I >NH + NH 3
:H2CONH2 CH2CO
considerable effervescence, as ammonia is liberated and succimmide
formed by ring closure. Yield, 2-5 g.

Benzamide. C6H5CONH2. (Method 2(b), p. 117.)


Required: Concentrated ammonia, 10 ml.; benzoyl chloride,
2 ml.
Carry out this preparation in precisely the same way as the
above preparation of oxamide, using 2 ml. (2-4 g.) of benzoyl
chloride instead of the ethyl oxalate, and observing the same
precautions. Considerably more heat is generated in this reac-
tion; therefore hold the cork very securely in position during
the shaking. After vigorous shaking for 15 minutes, no trace of
oily benzoyl chloride remains. Filter off the fine flakes of
benzamide, wash with cold water, and then recrystallise from hot
water: yield, 1-5 g. Colourless crystals, m.p. 130°.
i2o PRACTICAL ORGANIC CHEMISTRY
Hydrolysis of Benzamide. When acid amides are hydrolysed,
the corresponding acid and ammonia are formed. Consequently the
hydrolysis, which is extremely slow with water alone, is hastened con-
C6H6CO NH 2 + H O H - C6H5COOH + NH 3
siderably by the addition of either caustic alkalis (which give the alkali
salt of the acid and liberate ammonia) or mineral acids (which neutralise
the ammonia and liberate the organic acid). Caustic alkalis usually
effect the more rapid hydrolysis, and their use is to be preferred.
Place i g. of benzamide and 15 ml. of 10% aqueous sodium
hydroxide solution in a ioo ml. conical flask fitted with a reflux water-
condenser, and boil the mixture gently for 30 minutes, during which
period ammonia is freely evolved. Now cool the solution in ice-water,
and add concentrated hydrochloric acid until the mixture is strongly
acid. Benzoic acid immediately separates. Allow the mixture to stand
in the ice-water for a few minutes, and then filter off the bcnzoic acid
at the pump, wash with cold water, and drain. Recrystallise from hot
water. The benzoic acid is obtained as colourless crystals, m.p. 121°,
almost insoluble in cold water: yield, 0-8 g. (almost theoretical).
Confirm the identity of the benzoic acid by the tests given on p. 347.
Mercury Benzamide. (C6H5CONH)2Hg. (Semi-micro Scale.)
Acid amides have weakly amphoteric properties, and thus give salts such as
C6H6CONH2,HC1 with strong acids, and salts of the type C 6 H 5 CONHNa with
strong bases. These compounds have to be prepared at low temperatures to
avoid hydrolysis, and are difficult to isolate. The mercury derivatives can,
however, usually be readily prepared, because mercuric oxide is too feebly
basic to cause hydrolysis of the amide, and the heavy mercuric derivatives
crystallise well.
Required: Mercuric oxide, i g.; benzamide, o-8 g.; ethanol, 10 ml.
Add i g. of finely powdered mercuric oxide and o-8 g. of benzamide
to 10 ml. of ethanol, and boil the mixture under a reflux water-condenser
for 30 minutes. Now filter the hot solution through a fluted filter-
2C 6 H 5 CONH 2 + HgO = (C 6 H 5 CONH) 2 Hg + H2O
paper to remove unchanged mercuric oxide: if a fine suspension of the
oxide passes through with the first portion of the filtrate, return the
latter to the filter, when the remainder of the ethanolic solution will
pass through as a clear filtrate. Cool the latter in ice-water, where-
upon colourless crystals of mercury benzamide will separate. Finally
filter the crystals at the pump, wash with a small quantity of ethanol,
and then drain and dry. M.p. 222-223°: yield, 0-3 g. The mercury
benzamide so obtained may be recrystailised from hot ethanol, but this
is not necessary.
Nitriles (or Cyanides).
Aliphatic nitriles (or alkyl cyanides) can be prepared by the following methods:
PREPARATIONS 121
(1) Dehydration of the corresponding acid amides. This process usually
requires phosphorus pentoxide (correctly termed phosphoric anhydride) as a
dehydrating agent.
CH 3 CONH 2 — H1O -> CH 8 CN
Acetamide Acetonitrile
(2) By the action of potassium cyanide on the corresponding alkyl halide.
CH, I + K CN -* CH3CN + KI
NOTE.—Silver cyanide in these circumstances gives the isocyanide, CH3NC.
(3) By the direct addition of hydrogen cyanide to aldehydes and ketones,
giving cyanhydrins:
CH3CHO 4- HCN = CH3CH(OH)CN
Acetaldehyde cyanhydrin (Lactonitrile)
(CHa)2CO H- HCN = (CH8),C(OH)CN
Acetone cyanhydrin (a-Hydroxy-isobutyronitrile)
By this method, the nitrile of an oc-hydroxy acid is necessarily obtained.
Aromatic nitriles (or aryl cyanides) can be obtained by methods (i) and (3),
but not by method (2). In addition, aromatic nitriles can be prepared by two
other methods, (a) from the corresponding diazo compound by Sandmeyer's
Reaction (p. 189), (b) by fusing the corresponding sulphonic acid (or its salts)
C 4 H 6 SO8K + K CN -> C.H,CN + K2SO3
with potassium cyanide.

Acetonitrile (Methyl Cyanide). CH3CN. (Method i.)


Required: Acetamide, 20 g.; phosphorus pentoxide, 35 g.
In view of the great avidity of phosphorus pentoxide for water,
the apparatus used in this experiment should be assembled before
the pentoxide is weighed out. Fit a 500 ml. bolt-head flask to a
water-condenser (see Fig. 59, p. ioo). Disconnect the flask, then
twist some glazed paper into the form of a cone, and push the
narrow end of the latter (slightly opened) into the neck of the
flask. Using a rough balance, weigh out on pieces of glazed
paper first 20 g. of dry acetamide, and then (as quickly as
possible) 35 g. of phosphorus pentoxide. With the aid of a
spatula, tip the pentoxide without delay down the paper cylinder
into the flask, then add the acetamide similarly, remove the
paper, and at once cork the flask and mix the contents by
gentle shaking. (Before throwing away the paper used for
weighing the pentoxide, wet it thoroughly, otherwise residual
pentoxide may cause it to smoulder and possibly inflame.) Now
heat the flask by direct application of a Bunsen burner, using
however a luminous smoky flame, and applying it uniformly over
the bottom of the flask. The acetamide melts and then the
122 PRACTICAL ORGANIC CHEMISTRY
mixture starts to effervesce gently. Adjust the heating so that
the acetonitrile distils slowly over; use a small conical flask as a
receiver, and continue heating until no more distillate can be
readily obtained.
The crude acetonitrile contains as impurity chiefly acetic acid,
arising from the action of phosphoric acid on the acetamide.
Therefore add to the nitrile about half its volume of water, and
then add powdered dry potassium carbonate until the well-shaken
mixture is saturated. The potassium carbonate neutralises any
acetic acid present, and at the same time "salts out" the other-
wise water-soluble nitrile as a separate upper layer. Allow to
stand for 20 minutes with further occasional shaking. Now
decant the mixed liquids into a separating-funnel, run off the
lower carbonate layer as completely as possible, and then pour off
the acetonitrile into a 25 ml. distilling-flask into which about
3-4 g. of phosphorus pentoxide have been placed immediately
before. Fit a thermometer and water-condenser to the flask and
distil the acetonitrile slowly, collecting the fraction of b.p. 79-82°.
Yield 9-5 g. (12 ml.).
Acetonitrile is a colourless liquid, of b.p. 82° and d, 0790. It
has a faint but pleasant odour: if a sample has a faint odour of
mice, it indicates the presence of unchanged acetamide.
For reactions of acetonitrile, see p. 360.
Hydrolysis of Acetonitrile. Nitriles, like acid amides, undergo hydro-
lysis to give the corresponding carboxylic acid and ammonia. Consequently
CH 3 CN + 2H 2 O = CH3COOH + NH 3
the hydrolysis (which is extremely slow with hot water alone) is hastened
considerably by the presence of caustic alkalis or of mineral acids. The
aliphatic nitriles, being soluble in water, are readily hydrolysed by sodium hy-
droxide or by hydrochloric acid. The aromatic nitriles (such as benzonitrile,
C 6 H 5 CN) are almost insoluble in water and, although usually readily hydrolysed
by alkalis, are only very slowly hydrolysed by hydrochloric acid: sulphuric acid
(70%), however, causes rapid hydrolysis but there are practical objections
to its use (p. 193). Consequently students are recommended to use 10%
aqueous sodium hydroxide for hydrolysing nitriles generally, increasing the
concentration of the hydroxide to 15 or 20% for very stable nitriles.
Boil a mixture of 5 ml. (4 g.) of acetonitrile and 75 ml. of 10%
aqueous sodi um hydroxide solution in a 200 ml. flask under a reflux water-
condenser for 30 minutes, when hydrolysis will be complete. Detach
the condenser and boil the solution in the open flask for a few minutes
to drive off all free ammonia. Then cool the solution, and add dilute
sulphuric acid (i volume of concentrated acid: 2 volumes of water)
until the solution is distinctly acid to litmus-paper. Fit the flask to a
PREPARATIONS 123
water-condenser by means of a bent delivery (or "knee") tube, and
distil off about 10-15 ml. of the liquid. Confirm the presence of acetic
acid in this distillate by the tests given on p. 347.

Urea (or Carbamide). CO(NH2)2.


Urea (the diamide of carbonic acid) can be prepared by the historic method
of Wohler. When an aqueous solution of ammonium cyanate is allowed to
stand, the cyanate undergoes molecular rearrangement to urea, and an
equilibrium mixture containing about 93% of urea is thus formed. Urea is
NH 4 CNO ^ NH 2 CONH 2
less soluble in water than ammonium cyanate; therefore if the solution is
evaporated, urea begins to separate, and consequently the ammonium cyanate
undergoes steady conversion to urea in order to maintain the above equilibrium.
Ultimately, if the solution is evaporated to dryncss, the conversion to urea
becomes complete.
Ammonium cyanate, because of its instability in solution, is usually prepared
(NH 4 ) 2 SO 4 + 2KCNO = 2NH 4 CNO + K 2 SO 4
by mixing aqueous solutions of ammonium sulphate and potassium cyanate.
Complete evaporation then gives a mixture of potassium sulphate and urea,
from which the urea may be extracted with hot absolute ethanol, in which
potassium sulphate is insoluble.
Required: Ammonium sulphate, iog.; potassium cyanate, 12 g.
Add io g. of ammonium sulphate and 12 g. of potassium
cyanate to 75 ml. of water contained in an evaporating-basin.
Evaporate the mixed solution to dryness on a water-bath. During
the evaporation, a crust of potassium sulphate crystals forms on
the surface of the solution, and must be repeatedly broken by
stirring with a glass rod, otherwise the evaporation, which even
in favourable circumstances takes 4-5 hours, becomes extremely
slow: the stirring also prevents any solid material from creeping
over the edge of the basin. It is essential that the evaporation be
continued until the solid residue is completely dry. Now transfer
the residue to a ioo ml. flask fitted with a reflux water-condenser,
add 40 ml. of absolute ethanol, and boil gently for 5-10 minutes
in order to extract the urea. Filter the boiling solution through
a small fluted filter-paper, and cool the filtrate in ice-water. Urea
separates in colourless crystals, which when filtered at the pump,
drained and dried, have m.p. 132°: yield, 4 g. A small second
crop may be obtained by evaporating the ethanolic filtrate to about
io ml., and again cooling in ice-water.
Urea is a monacidic base, and forms a characteristic nitrate,
CO(NH 2 ) 2 ,HNO 3 , and oxalate, 2 CO(NH 2 ) 2 ,(COOH) 2 ,2H 2 O. To
prepare the nitrate, dissolve i g. of urea in about 5 ml. of
i2 4 PRACTICAL ORGANIC CHEMISTRY
water, and add 2 ml. of concentrated nitric acid. White crystals
of the nitrate separate almost immediately. Filter at the pump,
drain thoroughly, reject the filtrate, and then wash with a few ml.
of ethanol and ether in turn.
The oxalate is prepared in a similar way, using a solution of
!•2 g. of oxalic acid in about 15 ml. of water. On stirring the
mixed solutions with a rod, the oxalate crystallises out.
The chief disadvantage of the above preparation of urea is the long time
required for the complete evaporation of the mixed solutions, particularly as
occasional stirring is required throughout this operation. A more rapid
evaporation is obtained if ammonium chloride is used instead of the sulphate,
as the potassium chloride formed is more soluble in water than potassium
sulphate: the chloride is, however, slightly soluble in ethanol, and an impure
sample of urea is thus obtained. The following preparation of monophenyl-
urea (Method i) may well be substituted for that of urea, as the reaction in-
volved (molecular rearrangement of the cyanate of an amino compound) is the
same, but since the monophenyl-urea is insoluble in cold water, the long
evaporation is avoided.
For reactions of urea, see p. 362; for estimation, pp. 458, 520.
When the potassium cyanate used in the above preparation is replaced by
potassium thiocyanate (or sulphocyanide), the ammonium thiocyanate formed
undergoes partial rearrangement to thiourea (or sulpho-urea). Even above
NH 4 CNS ^ NH 2 CSNH 2
100°, however, the conversion into tjiiourea is incomplete, and the method does
not readily give a satisfactory preparation of thiourea.

Monophenylurea. C6H4NH-CO-NH2. (First Method.)


Mono-substituted and unsymmetrical di-substituted ureas may be prepared
by a modification of Wohler's urea synthesis, salts of primary or secondary
amines being used instead of the ammonium salt for interaction with potassium
cyanate. Thus when an aqueous solution containing both aniline hydrochlor-
ide and potassium cyanate is heated, aniline cyanate is first formed, and then
C,H 5 NH a ,HCl H- KCNO = C 6 H 6 NH 21 HCNO + KCl
C 6 H 5 NH 2 ,HCNO = C 9 H 6 NHCONH 2
by the usual molecular rearrangement is converted into monophenyl-urea.
Required: Aniline hydrochloride, 5 g.; potassium cyanate, 4 g.
Dissolve 5 g. of aniline hydrochloride in 120 ml. of hot
water contained in a 200 ml. conical flask and then add 4 g. of
potassium cyanate. Heat the solution on a water-bath for 30
minutes, adding about 1-2 g. of animal charcoal towards the
end of the heating if a slight turbidity has developed. Now bring
the solution quickly to the boil over a gauze, and filter it at the
pump, using a Buchner funnel and flask which have been pre-
heated by the filtration of some boiling distilled water. The clear
PREPARATIONS 125
filtrate on cooling deposits fine colourless crystals of monophenyl-
urea. Filter off at the pump and then recrystallise from hot
water: slow cooling of the hot aqueous solution causes the
monophenylurea to separate in large crystals. Yield, 3*0-3-5
g.;m.p. 147°.
Monophenyl- and Diphenyl-urea. (Second Method.)
These substances, having the formula C 6 H 5 NHCONH, and OC(NHC.H 5 ) 2
respectively, are both formed when an aqueous solution of urea and aniline
hydrochloride is heated. Their subsequent separation is based on the fact
that diphenylurea is insoluble in boiling water, whereas monophenylurea is
readily soluble. The formation of these compounds can be explained as follows.
When urea is dissolved in water, a small proportion of it undergoes molecular
rearrangement back to ammonium cyanate, an equilibrium thus being formed.
NH,CONHt ^ NH 4 CNO
The ammonium cyanate then reacts with the aniline hydrochloride giving
aniline cyanate which, as in the previous preparation, gives in turn monophenyl-
urea.
NH 4 CNO + C 6 H 6 NH 2 ,HC1 = NH 4 Cl + C 6 H 5 NH 2 ,HCNO
C 6 H 5 NH 2 ,HCNO = C 6 H 6 NHCONH 2
A portion of the monophenylurea then reacts with the aniline (formed
by the hydrolysis of the aniline hydrochloride or cyanate) to give diphenyl-
urea and ammonia, a reaction which probably proceeds through the
C 6 H 6 NH-CO-NH 2 + H 2 NC 6 H 6 = C 6 H 5 NH-CO NHC 0 H 5 + NH 3
intermediate formation of an unstable addition product of the formula
C 6 H 6 NHC(OH)(NH 2 )NHC 6 H 6 . The relative amounts of the monophenyl-
and the diphenylurea formed will therefore depend chiefly on the time during
which the aqueous solution is heated.

Required: Aniline hydrochloride, 12 g.; urea, 6 g.


Dissolve 12 g. of aniline hydrochloride and 6 g. of urea
in 50 ml. of warm water, and then filter the solution through a
fluted filter to remove any suspended impurities which may
have been introduced with the aniline hydrochloride. Transfer
the clear filtrate to a 200 ml. conical flask, fit the latter with
a reflux water-condenser, and boil the solution gently over a
gauze for about i j hours. Crystals of diphenylurea usually
start to separate after about 30-40 minutes' boiling. Occasionally
however, the solution becomes supersaturated with the diphenyl-
urea and therefore remains clear: in this case, if the solution is
vigorously shaken after about 40 minutes* heating, a sudden
separation of the crystalline diphenyl compound will usually
occur. The further deposition of the crystals during the re-
126 PRACTICAL ORGANIC CHEMISTRY
mainder of the heating may cause the solution to "bump": if
this bumping becomes too vigorous, remove the flame for a few
minutes to allow the solution to cool slightly and thus to ensure
it is not superheated, then add some fragments of unglazed
porcelain down the condenser, and continue the heating.
When the I^ hours' boiling is complete, preheat a Buchner
funnel and flask by pouring some boiling water through the
funnel with the filter-paper already in position, and then quickly
filter the boiling solution. Transfer the filtrate to a beaker to
cool, and then wash the insoluble residue of diphenylurea on the
filter twice with hot water, and drain thoroughly. Cool the
filtrate in ice-water; the monophenylurea separates as colourless
needles. Filter at the purnp and drain well. Recrystallise the
crude product from boiling water, as in the previous preparation.
Yield of monophenylurea, 2-5-3 g.; m.p. 147°.
The insoluble residue of diphenylurea from the original
filtration is chemically almost pure. It may be recrystallised
from hot rectified spirit or ethanol, a process which will be
necessary if the material contains fragments of porcelain. When
using either of these solvents, however, the hot solution should
be filtered* at the pump using a small Buchner funnel and flask
which again have been preheated by the filtration of some of
the hot solvent, as the solution when cooled rapidly deposits
the diphenylurea. Sym-Diphenylurea (or carbanilide) is thus
obtained as fine colourless crystals, m.p. 237°; yield, 1-1-5 g.
Benzylthiouronium Chloride.
Thiourea, unlike urea, readily reacts in the tautomeric form (I) in the presence
of suitable reagents, particularly alkyl halides: thus benzyl chloride reacts with
/NH, /N H,

C6H6CH8Cl -f HS-C + C8H6CH2S-C' Cl


X
(I) NH NsJH1
(ID
thiourea in ethanolic solution to give benzylthiouronium chloride (II), sometimes
known as S-benzylthiouronium chloride, a salt which is stabilised by resonance.
Such salts on acid hydrolysis give the corresponding thiols, e.g., C6H5CH8SH,
which can thus be readily prepared from the halides. Furthermore, the salt
(II) is widely employed to identify carboxylic and other acids as their crystalline
benzylthiouronium salts (pp. 349-353).

* Alternatively a preheated conical funnel and fluted filter may be used, and
the filtrate collected directly in a conical flask.
PREPARATIONS 127
Required: Benzyl chloride, 8-3 g.; thiourea, 5 g.
Add in turn benzyl chloride (8-3 g., 8-0 ml.) and powdered
thiourea (5 gm.) to 10 ml. of 95% ethanol in a ioo ml. flask
fitted with a reflux condenser. Warm the mixture on the water-
bath with gentle shaking until the reaction occurs and the
effervescence subsides; then boil the mixture under reflux for
30 minutes. Cool the clear solution in ice-water, filter off the
crystalline deposit of the benzylthiouronium chloride at the
pump, wash it with ice-cold ethyl acetate, and dry in a desic-
cator. Yield, 11-12 g., m.p. 170-174°. The white product is
sufficiently pure for use as a reagent. It is very soluble in cold
water and ethanol, but can be recrystallised by adding ethanol
dropwise to a boiling suspension in ethyl acetate or acetone until
a clear solution is just obtained, and then rapidly cooling.
Hofmann's Primary Amine Synthesis.
The preparation of pure primary amines by the interaction of alkyl halides
and ammonia is very difficult, because the primary amine which is formed
reacts with unchanged alkyl halide to give the secondary amine: the latter
C 2 H 5 I + HNH 2 -> C 2 H 5 NH 2 + HI
C 2 H 5 I + HNC 2 H 5 -> (C 2 H 5 ) 2 NH -f HI
C 2 H 5 I + HN(C 2 H 5 ) 2 -> (C 2 H 5 ) 3 N + HI
C 2 H 5 I -K (C 2 Hs) 3 N -> (C 2 H 5 ) 4 NI
similarly gives the tertiary amine, which unites with unchanged alkyl halide
to give the quaternary ammonium halide. The preparation of pure primary
amines is carried out therefore by special methods, such as the reduction of
oximes (p. 93) and of nitro-compounds (pp. 132, 161). A third method due to
Hofimann is based on the action of bromine on acid amides, with subsequent
alkaline hydrolysis. The reactions involved probably proceed as follows.
Acetamide when treated with bromine forms acetbromoamide, CH 3 CONHBr,
which in NaOH solution gives the ionised sodium acetbromoamide, CH 3 CONBr
+ Na. The anion loses B"r with simultaneous migration of the CH 3 group to
the nitrogen, giving methyl isocyanate, which
CH 3

C-O -> CH 3 N-C-O -> CH 3 N-C-O > CH 3 NH 2

undergoes hydrolysis to methylamine.


128 PRACTICAL ORGANIC CHEMISTRY
A certain amount of hydrolysis of the original acetamide to acid and ammonia
always occurs, and the final amine always contains traces of ammonia. This
is separated by extracting the mixed anhydrous hydrochlorides with absolute
ethanol, which dissolves the amine hydrochloride but not the ammonium
chloride: filtration of the hot ethanolic extract removes the ammonium chloride,
whilst the amine hydrochloride crystallises readily from the filtrate on cooling.
Hofmann's amine synthesis can be applied to both aliphatic and aromatic
carboxylic acid amides, benzamide, C 6 H 6 CONH 8 , thus giving aniline,
C.HBNH,.
METHYLAMINE HYDROCHLORIDE. CH3NH21HCl.
Required: Acetamide, 12 g.; bromine, 10-8 ml.; sodium hyd-
roxide, 36 g.
Dissolve 36 g. of sodium hydroxide in 160 ml. of water con-
tained in a 500 ml. conical flask, and chill the stirred solution to
0-5° in ice-water. Nov/ add io-8 ml. (32-4 g.) of bromine slowly
to the stirred solution (exercise care in manipulating liquid
bromine!): during this addition the temperature rises slightly, and
it should again be reduced to 0-5°. Add a solution of 12 g. of
acetamide in 20 ml. of water, in small portions, to the stirred
hypobromite solution so that the temperature of the mixture does
not exceed 20°: the sodium acet-bromoamide is thus obtained in
the alkaline solution. Now remove the flask from the ice-water,
and set it aside at room temperature for 30 minutes.
Meanwhile assemble the apparatus shown in Fig. 62, or that
in Fig. 23(0), p. 45, having a distilling-flask of at least 500 ml.
capacity in either case. If an ordinary condenser C (Fig. 62) is
employed, fit the lower end of the
condenser by means of a short
piece of rubber tubing to a small
inverted funnel. Arrange the
latter so that its lip is just below
the surface of 25 ml. of concen-
trated hydrochloric acid diluted
with 75 ml. of water contained
in a 250 ml. beaker B: the hydro-
chloric acid is thereby prevented FIG. 62.
from being sucked back into the
condenser during the subsequent distillation. If the ground-glass
apparatus shown in Fig. 23(0) is used, the inverted funnel can be
similarly attached to the end of the adaptor.
Transfer the solution into the flask, add some unglazed porcelain,
and support the flask over an asbestos-covered gauze. Heat the
solution cautiously with a Bunsen flame so that the temperature
PREPARATIONS 129
rises slowly. When a brisk effervescence occurs (at about 70-80°),
remove the flame until the reaction subsides. Methylamine is
evolved, and is absorbed by the hydrochloric acid in the beaker
B. Then distil the solution in the flask carefully, keeping it boiling
smoothly and uniformly so that no methylamine vapour escapes
absorption in the hydrochloric acid, and at the same time so that
the acid shows no marked tendency to rise in the funnel.
After boiling for 30 minutes, the distillation of the amine may
be considered complete. Concentrate the hydrochloric acid
solution by placing it in a 250 ml. distilling-flask connected with a
water-condenser, and distilling carefully until about 30 ml. re-
main. Then transfer this residual solution to a small evaporating-
basin, and evaporate to dryness on a boiling water-bath. (Yield
of crude dry material, about 11 g.) Rapidly break up the dry
solid (which consists of methylamine hydrochloride together with
a small amount of ammonium chloride), and transfer it without
delay to a 150 ml. round-bottomed flask fitted with a reflux
water-condenser. Add about 60-70 ml. of absolute ethanol (in
which ammonium chloride is insoluble), and boil the mixture for
5 minutes. Then pour the hot supernatant liquid quickly through
a small fluted filter-paper into a conical flask. Again extract the
undissolved residue with a further 20 ml. of absolute ethanol, and
cool the united ethanolic filtrates: colourless crystals of methyl-
amine hydrochloride separate out. Filter off the crystals at the
pump, and, since they are deliquescent, transfer them quickly to a
weighed bottle or specimen-tube: the methylamine hydrochloride
may be finally dried by placing the tube in a desiccator. The yield
of the recrystallised material should be about 5 g.; if the ethanolic
filtrate from this first crop is concentrated by distillation to about
20 ml. and then cooled, a second crop of methylamine hydro-
chloride, weighing about 3 g., can be similarly isolated.
CAUTION.—If the ethanol used to extract the methylamine hydrochloride is not
"absolute," i.e., if it contains traces of water, considerably less than the above
suggested quantity will be required for the extraction, because the solubility
of the hydrochloride will be markedly increased by the water present. The
recrystallised material will no*v, however, contain traces of ammonium chloride.
Glycine (Ammo-acetic Acid). NH2-CH2COOH.
Glycine is the simplest member of a large and very important class of com-
pounds, the a-amino-carboxylic acids. There are many different methods
available for the synthesis of amino-acids, but glycine can be readily prepared by
the action of an excess of ammonia on chloroacetic acid:
ClCH2COOH + 2NH 8 = NH 2 -CH 2 COOH + NH 4 Cl
(Note that although glycine is conveniently written as above, it is actually a
130 PRACTICAL ORGANIC CHEMISTRY
zwitter-ion, NH 3 -CH 2 COO: consequently although the ammonium salt of
glycine may De initially formed in the above reaction, it readily dissociates
during the subsequent concentration of the solution to give the free glycine).
The glycine so formed has to be separated from the ammonium chloride, and
the salt-like nature of the zwitterion precludes
"NH1-CHiCOO^ the use of most organic solvents for this purpose.
\^ / The mixture can be treated with copper hydroxide
\ / (cf. p. 382) and the glycine precipitated as the
Cu insoluble non-ionic cupric complex (annexed
/ \ formula): the latter can then befilteredoff, washed
and decomposed in aqueous suspension by hydro-
gen sulphide. The following more convenient
method is based on the fact that glycine is much
less soluble than ammonium chloride in methanol.
Note that the amino-acids, because of their salt-like nature, usually decompose
on heating, and therefore seldom have sharp melting-points. Furthermore, all
naturally occurring amino-acids are a-amino-acids, and consequently, with the
exception of glycine, can exist in optically active forms.
Required: Chloroacetic acid, 15 g.; ammonia solution (d,
o-88o), 300 ml.
Add 15 g. of chloroacetic acid to 300 ml. of aqueous am-
monia solution (d, 0-880) contained in a 750 ml. conical flask.
(The manipulation of the concentrated ammonia should prefer-
ably be carried out in a fume-cupboard, and great care taken to
avoid ammonia fumes.) Cork the flask loosely and set aside
overnight at room temperature. Now concentrate the solution
to about 30 ml. by distillation under reduced pressure. For this
purpose,* place the solution in a suitable distilling-flask with some
fragments of unglazed porcelain, fit a capillary tube to the neck
of the flask, and connect the flask through a water-condenser
and receiver to a water-pump: then heat the flask carefully
on a water-bath. Make the concentrated solution up to 40 ml.
by the addition of water, filter, and then add 250 ml. of methanol.
Cool the solution in ice-water, stir well, and set aside for ca.
i hour, when the precipitation of the glycine will be complete.
Filter off the glycine through a Buchner funnel, and then
transfer it to a beaker, add 80 ml. of methanol and stir the mixture
well. Then filter again, wash the glycine on the filter with a small
quantity of ether, drain and dry.
The glycine so obtained is almost pure. To remove traces
of ammonium chloride, however, dissolve the glycine in 30 ml.
of water, and then reprecipitate by the addition of 200 ml. of
methanol. Cool the product in ice-water with stirring, and then
* Cf. p. 28.
PREPARATIONS 131
filter again through a Buchner funnel. The glycine is obtained
as a fine colourless crystalline powder, which has m.p. 230-231°
(with decomposition) if it is placed in a bath preheated to ca.
210° and the temperature then increased fairly rapidly. Yield,
7-5-8-0 g.
Aliphatic Nitro-compounds.
Since aliphatic hydrocarbons (unlike aromatic hydrocarbons, p. 155) can be
directly nitrated only under very special conditions, indirect methods are usually
employed for the preparation of compounds such as nitroethane, C 8 H 6 NO 2 .
When ethyl iodide is heated with silver nitrite, two isomeric compounds are
formed, and can be easily separated by fractional distillation. The first is the
true ester, ethyl nitrite, C1H5ONO, of b.p. 17°: its identity is shown by the action
of hot sodium hydroxide solution, which hydrolyses it, giving ethanol and

C 2 H 5 ONO + NaOH -> C 2 H 5 OH + NaNO 2


sodium nitrite. The second compound is nitroethane, C a H 6 NO a , of b.p. 114°:
its identity is clearly shown by the action of reducing agents, which convert it
into ethylamine, C 2 H 6 NH 2 , thus proving the presence of a nitrogen-carbon
C 2 H 5 NO 2 + 6H - C 2 H 5 NH 2 + 2H 2 O
link in the nitro-ethane. This formation of the isomeric nitrite ester and nitro-
paraffin is characteristic of the reaction of the lower alkyl halides with silver
nitrite.
Nitromethane, CH 3 NO 2 , the first member of the homologous series, can,
however, be readily prepared by a special reaction.* When equimolecular
amounts of sodium nitrite and sodium monochloroacetate are heated together
in aqueous solution, the chlorine in the monochloroacetate is replaced by the
nitro group, and the sodium nitroacetate thus formed undergoes hydrolysis
followed by decarboxylation:
NaNO 2 + ClCH8COONa = NaCl + NO 8 CH 2 COONa
2NO 2 CH 2 COONa + H 2 O = 2NO 8 CH 3 + Na 2 CO, + CO8
The characteristic property of aliphatic nitro-compounds of the type
RCH 2 NO 2 and R 2 CHNO 2 is that they are pseudo-acids, i.e., whereas they are
neutral in the normal form (A), they are able by tautomeric change under the
influence of alkali to give the acidic hydroxy form (B) which thus in turn gives
the sodium salt (C). When this sodium salt is treated with one equivalent of
hydrochloric acid, the acid form (B) is at once regenerated, and then more slowly
reverts to the more stable normal form (A).
.O X)H NaOH ONa
CH 1 CH 8 -Nf^ 7-* CH 8 CHrN/ > CH 3 CHtN/
O "1O HCi O
(A) (B) (C)

* This reaction is general for a-chloro-carboxylic acids: of these, however


only monochloroacetic acid is readily and cheaply obtainable, and it also gives
the highest yielcTof the nitrohydrocarbon.
132 PRACTICAL ORGANIC CHEMISTRY
Nitromethane. CH3NO2.
Required: Monochloroacetic acid, 50 g.; anhydrous sodium
carbonate, 30 g.; sodium nitrite, 36-5 g.
Dissolve 50 g. of monochloroacetic acid in ioo ml. of
water contained in a 500 ml. round-bottomed bolt-head flask, and
then neutralise the solution by the cautious addition of 30 g. of
finely powdered anhydrous sodium carbonate. For this purpose,
add the sodium carbonate in small quantities (about i g.) at a
time, preferably with the aid of a spatula, and shake the solution
gently around after each addition to facilitate the evolution of
carbon dioxide: a clear solution is thus maintained throughout,
whereas the rapid addition of large quantities of the carbonate
produces lumps of material which are subsequently difficult to
dissolve. Now dissolve 36-5 g. of sodium nitrite in 50 ml. of
water with gentle heating, cool the solution thoroughly in ice-
water, and then add it with shaking to that of the sodium mono-
chloroacetate. Add some fragments of unglazed porcelain, and
then fit the flask with a delivery-tube of moderately wide bore
connected in turn to a water-condenser (as in Fig. 59, p. ioo, or,
better, in Fig. 23(0), p. 45). Support the flask over a gauze, and
then heat it gently with a small Bunsen flame. The solution
slowly becomes yellow in colour, then greenish and finally a
yellowish-brown, when a vigorous effervescence starts: at once
remove the Bunsen flame, and allow the reaction to proceed
spontaneously, carbon dioxide being evolved and the solution
boiling vigorously. When the reaction subsides, replace the
Bunsen flame and maintain a steady boiling. Nitromethane distils
over in the steam and separates as a colourless oil at the bottom
of the distillate: since nitromethane is slightly soluble in water,
stop the distillation as soon as drops of nitromethane can no
longer be detected in the distillate leaving the condenser. Trans-
fer the distillate to a separating-funnel, and carefully run off the
lower layer of nitromethane and then dry it over anhydrous
sodium sulphate for 30 minutes. Filter the dry nitromethane
(preferably through a small dry Buchner funnel), transfer it to a
30 ml. distilling-flask fitted with a water-condenser, and then
slowly distil, collecting the fraction of b.p. 100-102°.
In view of the small volume of nitromethane to be manipulated, the
crude nitromethane may be extracted from the aqueous distillate with
ether (30-40 ml.). Dry the ethereal extract over sodium sulphate, filter
through a fluted filter-paper, and then distil off the ether on a water-bath
with the usual precautions (Fig. 64, p. 163; Fig. 23(E), p. 45): finally dis-
til the residual nitromethane.
PREPARATIONS 133
Nitromethane is obtained as a colourless liquid, of b.p. 101°
and d, 1-16: yield, 10 g.
Reactions of Nitromethane. (i) Nitromethane, although only
slightly soluble in cold water, is freely soluble in sodium hydroxide
solution, the alkaline solution slowly becoming yellow in colour.
(2) Place a few drops of nitromethane in a test-tube, add about
3 times as much concentrated hydrochloric acid, and then a piece of
granulated tin. The tin dissolves in the acid and the nascent hydrogen
produced reduces the nitromethane to monomethylamine:
CH 3 NO 2 4-6H = CH 3 NH 2 + 2 H 2 O
Moderate the reaction if necessary by dipping the tube in cold water.
When the tin has completely dissolved, cool the solution thoroughly, and
make alkaline by the addition of concentrated (30%) sodium hydroxide
solution. A strong ammoniacal smell of monomethylamine is pro-
duced, and white fumes form when the open end of the tube is placed
near an open bottle of concentrated hydrochloric acid. This formation
of methylamine proves that in the original nitromethane the nitrogen
atom is joined directly to the carbon.
(3) Dissolve O'5 g. of sodium in 10 ml. of anhydrous methanol
contained in a small conical flask: check the reaction at first by cooling
the flask in water to prevent evaporation of the methanol, but finally
warm the mixture gently to hasten the dissolution of the last traces
of sodium. Cool this solution of sodium methoxide, and then add
i ml. of nitromethane, and mix thoroughly. A gelatinous precipitate
of sodium nitromethane rapidly appears. Cool the mixture in ice-
water for 5 minutes, and then filter off the sodium derivative at the
pump, using a small dry Buchner funnel; drain quickly, and then
wash with a few drops of methanol, to remove traces of excess sodium
methoxide, again draining the white sodium derivative as quickly as
possible. Perform the following tests with this sodium derivative
whilst it is still damp with methanol:
(a) Dissolve a small portion of the sodium derivative in a few ml. of
water in a test-tube, and add one drop of ferric chloride solution. A
deep red coloration is produced, but rapidly disappears as the iron is
precipitated as ferric hydroxide. The sodium derivative (A) of the
nitromethane when dissolved in water undergoes partial hydrolysis,
/ONa /OH
CH2:N< + HOH TZ?! CH2:N< + NaOH
^O ^O
(A) (B)
giving sodium hydroxide and the free acid (B): the latter, like many
hydroxy compounds (compare phenols, p. 338), gives a marked color-
ation with ferric chloride.
(b) Dissolve the remainder of the sodium derivative in about 50 ml.
134 PRACTICAL ORGANIC CHEMISTRY
of cold water in a clean beaker. Add a drop of phenolphthalein solu-
tion. A deep pink coloration is produced, owing to the free sodium
hydroxide formed in the above hydrolysis. Now by means of a small
pipette or a fine glass tube, add very dilute sulphuric acid drop by drop
until the pink coloration is just discharged. In a few seconds the pink
coloration becomes again perceptible, and rapidly deepens in tint. The
sulphuric acid may again be added, and the process repeated several
times.
The addition of the sulphuric acid first neutralises the sodium hydrox-
ide, and then gives a weakly acidic and therefore colourless solution.
The sodium derivative (A) then undergoes further partial hydrolysis
in order to re-establish the original equilibrium, and the sodium
hydroxide thus formed again produces the pink coloration, which
increases in depth as the hydrolysis proceeds.
When the above tests have been completed, wash thoroughly with
water all apparatus contaminated with the sodium derivative, since the
latter, if allowed to dry, becomes very explosive.
(4) Dissolve a few drops of nitromethane in 10% sodium hydroxide
solution. Add a few crystals of sodium nitrite and shake. Now
add dilute sulphuric acid drop by drop. A brownish-red coloration
develops, but fades again when an excess of acid is added. The
sulphuric acid has thus liberated nitrous acid, which has in turn reacted
with the nitromethane to give a nitrolic acid, the sodium salt of which is
CH3NO2 + ONOH - CH(NO2):NOH + H2O
reddish-brown in colour, probably owing to mesomeric ions of the type:
O _ O-
O«-N-CH:N-O «--> O«-N:CH-N:O
An excess of sulphuric acid then converts the coloured sodium salt back
to the almost colourless nitrolic acid.
NOTE.—A secondary nitre-paraffin, such as 2-nitropropane, (CH 3 ) 2 CHNO 2 ,
when similarly treated gives a pseudo-nitrol, which dissolves in chloroform,
(CHj)2CHNO1 + HONO = (CH,),C(NO)NOt + H1O
producing a blue solution. A tertiary nitro-paraffin, such as trimethylnitro-
methane, (CHj)8CNOj, gives no reaction with nitrous acid.

The Sugars (or Carbohydrates).


The only sugars which the student is likely to meet in the course of ordinary
laboratory work are the two isomeric monosaccharides glucose (sometimes called
dextrose or grape sugar) and fructose (laevulose or fruit sugar) of formula
C6H11O1, and the three isomeric disaccharides sucrose (cane sugar), lactose (milk
sugar) and maltose (malt sugar) of formula C12H2xOn. It has been established
that sugars possess ring structures (I, II, IV), but nevertheless under certain
conditions the ring opens out to give a straight chain compound which may
possess either a free - CHO group (aldoses, such as glucose, III) or a free >CO
group (ketoses, such as fructose, V). Many of the characteristic reactions of
PREPARATIONS 135
particularly those of reduction and of osazone formation, are due to
these groups.
H OH HO H
V \/
I C •— \^ i L,J1U IMU L,W,U11 I UM1Ul-I

2
I
HCOH
I
HCOH 2 HCOH
I
2-i
\/
/"*
L> 2
I
CO
I
3 HOCH
I
HOCH
I
3 HOCH 3 HOCH
I I
3 HOCH
I o I o I I o I
4 HCOH I HCOH 4 HCOH 4 HCOH 4 HCOH
I I I I I
5 HC 1 HC 1 5 HCOH 5 HCOH 5 HCOH
I I I I
6 CH,OH CH1OH 6 CH8OH 6 CH, 1 6 CH1OH
a-Glucose p-Glucose Glucose P-Fmctose Fructose
(I)* (II)* (III) (IV)* (V)
It will be seen that the ring form of glucose can exist in two isomeric forms
<x and (3, which differ only with regard to the disposition of the H and the OH
groups around carbon atom i, since if the ring is regarded (for simplicity) as
being in the plane of the paper, a-glucose (I) may have this H atom above, and
the OH group below, the plane of the paper, whilst ^-glucose (II) will have the
H atom below, and the OH group above this plane. These ring structures for
a and {3-glucose can alternatively be represented by (VI) and (VII). a and

OH OH
(VI)* (VII)*
p-glucose, when dissolved in water, have different optical rotatory powers
(although they are not of course optical enantiomorphs, as the above
formulae show): the optical rotation of each solution changes slowly on stand-
ing, and the final value attained is identical in each case, i.e.. a mixture of both
forms in equilibrium is ultimately obtained from either a or p-glucose. The
difference between a- and (3-glucose disappears in the straight chain form (III),
and since it is in this form that glucose often appears to react, this difference
between the a and P forms can often be ignored in practical work. Fructose
exists similarly in two forms, determined by the disposition of the OH and
* Structures (I), (II) and (IV) are convenient projection formulae; formulae
such as (IV) and (VII) are more realistic representations, but even these are
only approximations as the rings are not flat.
136 PRACTICAL ORGANIC CHEMISTRY
the CH 2 OH groups around carbon atom 2, this difference again disappearing
in the straight chain form (V). It will be noted that carbon atom i in glucose
is concerned with the formation of the ring, and that when the latter opens
out, the free aldehyde group appears at this point. The grouping on carbon
atom i may conveniently be called the "potential aldehyde group," and that on
carbon atom 2 in the fructose molecule similarly the "potential ketone group."
For an elementary study of the supars, it is not suggested that the student
should remember the structure of the disaccharidcs: their chief and character-
istic reactions will, however, be readily understood if the following facts arc
borne in mind.
Sucrose on hydrolysis with dilute acids, or with the enzyme invertase (or " su-
crase," p. 514,) gives rise to one molecule of glucose and one molecule of fructose:

C12H22O11 + H2O = C 8 H 12 O 6 + C 6 H 12 O 6
sucrose glucose fructose

In the sucrose molecule, union takes place through carbon atom i of the glucose
molecule and carbon atom 2 of the fructose molecule: hence sucrose i? a non-
reducing sugar, since neither the potential aldehyde nor the potential ketone
grouping is now available for reaction. If glucose is represented as G-r, where
r is the potential aldehyde group, and fructose as F-r, where r is the potential
ketone group, then the sucrose molecule may be conveniently remembered as
G-r-r-F, indicating clearly that both the reducing groups are concerned in the
union of the two monosaccharide residues.
!Maltose on hydrolysis with dilute acids or with the enzyme maltase gives rise
to two molecules of glucose: only one of the potential aldehyde groups is
concerned in the union of the glucose molecules, and the structure of maltose
may therefore be represented as G-r-G-r. Maltose has thus one free potential
aldehyde group, and is therefore a reducing sugar, differing in this respect from
sucrose.
Lactose on hydrolysis gives glucose and an isomeric monosaccharide galactose,
which may be given the symbol Ga-r. The lactose molecule may be represented
as Ga-r-G-r, and it has therefore also a free potential aldehyde group and is a
reducing sugar like maltose.
A very important method of identifying reducing sugars is by means of the
osazones which they form with phenylhydrazine, C 0 U 6 NHNH 2 . These osazones
are bright yellow compounds, which exhibit characteristic crystalline forms
under the microscope. To explain the formation of the osazones of glucose
and fructose, the latter sugars are represented for simplicity by the straight
chain formulae ( I I I ) and (V) respectively. When glucose is treated with an
excess of phenylhydrazine (preferably in the presence of acetic acid), a soluble
phenylhydrazone (IIIA) is first formed by the condensation of one molecule of
phenylhydrazine with the - CHO group of the glucose. This is strictly analogous
to the formation of benzaldehyde phenylhydrazone from benzaldehyde (p. 229).
PREPARATIONS 137
(i) CHO -r H 2 XNHC 6 H 5 CH:NNHC«H 6 CH:NNHC 6 H 6 CH:NNHC,Hfi
I I I I
(z)CHOH CHOH CO -f H 2 NNHC 6 H 5 C:NNHC,H6
I I -2H I I
(CHOH)3 * (CHOH)3 > (CHOH), > (CHOH)8
I I I I
CH2OH CH2OH CH8OH CH2OH
(III) (UlA) (UlB) (IIIC)

Now phenylhydrazine will readily act as an oxidising agent, since it can accept
two hydrogen atoms from another compound, being itself reduced to aniline
and ammonia, C 6 H 5 NHNH 2 -f zH = C 6 H 5 NH 8 -f NH 8 . The second mole-
cule of phenylhydrazine therefore oxidises the secondary alcohol group
(> CHOH) of carbon atom (2) to a ketone (> C :O) group by removal of two hydro-
gen atoms, giving the compound (UlB). The free >C:O group of the latter
compound now condenses with a third molecule of phenylhydrazine, giving
the osazone of glucose, or phenyl-glucosazone (IIIc).
Fructose (V) under similar conditions gives first the phenylhydrazone (VA)
by the direct condensation of the >C:O group of carbon atom 2 with one
molecule of phenylhydrazine. The second molecule of phenylhydrazine then
oxidises the primary alcohol group of carbon atom I to the - CHO group by
removal of two atoms of hydrogen, which as before serve to reduce the phenyl-
hydrazine to aniline and ammonia. The compound (Vs) which is thus pro-
duced then undergoes direct condensation \vith the third molecule of phenyl-
hydrazine, giving the osazone of fructose, or fructosazone (Vc).
Now since the configuration of carbon atoms 3, 4 and 5 of glucose and
fructose are identical, it follows that glucosazone and fructosazone are identical
in all respects. The osazone is formed however more rapidly from fructose
than from glucose, and this difference in rate of formation may be used to
distinguish the two sugars, provided the reactions are carried out under strictly
parallel conditions (pp. 138, 338).
i CH,OH CH,OH CHO + HoNNHC 6 H 5 CH:NNHC.H8
I I I I
2CO + H 2 NNHC 6 H 5 C:NNHC6H5 CiNNHC 6 H 5 CrNNHC 4 H 6
I I -2H I I
(CHOH), » (CHOH), > (CHOH), * (CHOH),
I I I I
CH1OH CH,OH CH8OH CH8OH
(V) (VA) (VB) (Vc)
Both maltose and lactose, being reducing sugars, give osazones which differ
from one another and from glucosazone in crystalline form. Sucrose (G-r-r-F),
having no potential aldehyde or ketone grouping, does not form an osazone.

Glucosazone (Phenyl-glucosazone). C6H10O4(N-NHC6Hs)2.


In the preparation of osazones (as in the preparation of phenylhydrazones,
138 PRACTICAL ORGANIC CHEMISTRY
p. 229) the free phenylhydrazine base may be used directly. Condensation
occurs more readily and a cleaner product is obtained, however, if the reaction
is carried out in weakly acidic solution—preferably at about pH 5 (see foot-
note, p. 509). The phenylhydrazine base should therefore always be dissolved
in acetic acid for this purpose.
Phenylhydrazine is, however, frequently supplied in the form of its hydro-
chloride or sulphate, since these salts on exposure to light darken less rapidly
than the free base. If these salts are used, however, osazone formation is
unsatisfactory, partly because the mineral acid formed by hydrolysis of
C,H6NHNH,,HC1 ^ C6H6NHNH1 + HCl
the salt hydrolyse8 the glucosazone to glucosone, CHO-CO-(CHOH)8CH1OH.
Therefore if these salts are used, they should be mixed in solution with a small
excess of sodium acetate, whereby the pH of the solution is raised to approxi-
mately the required value. On the other hand, care should be taken not to
add too large an excess of sodium acetate, which by hydrolysis would make
the solution too alkaline: this can if necessary be corrected by the addition
of a few drops of acetic acid.
Required: Glucose, i g.; acetic acid, 2 ml.; phenylhydrazine,
2 ml.
Dissolve i g. of glucose (or fructose) in 5 ml. of water in a
boiling-tube. In another tube dissolve 2 ml. of glacial acetic acid
in 5 ml. of water, add 2 ml. of phenylhydrazine,* and shake until
a solution of phenylhydrazine acetate is obtained. Add this
solution (which is often opalescent) to the sugar solution, stir
gently with a glass rod, and then place the tube in a boiling
water-bath. The yellow osazone usually begins to crystallise out
after about 15 minutes' heating. Continue the heating (with
occasional stirring) for a total period of 45 minutes, then remove
the tube and cool by immersion in cold water. Filter the product
through a Buchner funnel, and wash it first with water and then
with a few ml. of methylated spirit, and drain thoroughly. Yield
of osazone from glucose, 1-5 g.'t If fructose is used, only 30
minutes' heating is necessary, and the yield of osazone is 1-8 g.,
i.e., almost theoretical.
Glucosazone is only slightly soluble in boiling ethanol or
methylated spirit: for recrystallisation therefore it is sufficient to
place about 0-5 g. of the crude material in a 150 ml. flask fitted
* If only the hydrochloride or sulphate of the base is available, dissolve
3 g. of crystalline sodium acetate (or 2 g. of the anhydrous acetate) in 12 ml.
of water, add 3 g. of the phenylhydrazine salt, warm gently until dissolved,
filter the solution if necessary* and then add to the sugar solution.
t If the reaction mixture is heated for i j hours, this yield is slightly increased.
The increase is too small, however, to warrant the extra time expended.
PREPARATIONS '39
with a reflux condenser, then to add about 75 ml. of methylated
spirit, and boil gently. The osazone dissolves slowly; filter the
hot solution through a fluted filter-paper (or a preheated Buchner
funnel), and allow the filtrate to cool slowly in order to ensure
good crystal formation.

(B) (C)
Glucosazone (Fructosazone) Maltosazone Lactosazone

FIG. 63.

If it is desired to observe the crystalline form of the osazone,


draw up in a glass tube a few drops of the cold filtrate containing
the fine crystals, and transfer to a microscope slide. Cover the
drops with a slip and examine under the microscope: unless the
filtrate has been cooled very slowly and thus given moderately-
sized crystals, the high power of the microscope will probably be
required. Note the fine yellow needles aggregated in the form of
sheaves. Compare with Fig. 63(A).
Then filter the remainder of the product at the pump, drain
and dry. The glucosazone is thus obtained as bright yellow
crystals, m.p. 204° with decomposition.
Maltosazone (Phenyl-maltosazone).
C12H2009(N.NHC6H5)2.
Required: Maltose, 2 g.; acetic acid, 2 ml.; phenylhydrazine,
2 ml.
Proceed as in the preparation of glucosazone, using for the first
solution 2 g. of maltose in 10 ml. of water, and for the second
solution 2 ml. of phenylhydrazine dissolved in a mixture of 2 ml.
of glacial acetic acid and 5 ml. of water. Heat in a boiling
water-bath for 30 minutes. Maltosazone is much more soluble
than glucosazone in hot water, and therefore does not separate
whilst the boiling-tube is still in the boiling water-bath. When
the heating is complete, either turn out the gas and allow the
tube to cool slowly while still in the bath, or alternatively place
HO PRACTICAL ORGANIC CHEMISTRY
the tube in a small beaker of boiling water and there let it cool:
the maltosazone crystallises as the solution cools. (If the solution
is cooled rapidly, the osazone separates as minute crystals, and
subsequent filtration at the pump will be very slow.) Finally
complete the cooling by immersing the boiling-tube in cold
water, and then filter off the maltosazone at the pump, wash with
a few ml. of cold water, and drain. (Yield, 1-2 g.). Recrystallise
the osazone from a small quantity of boiling water. Allow the
solution to cool very slowly as before, and examine the crystals
as directed in the previous preparation. Note the long narrow
plates, and compare them with Fig. 63(8). Filter off the re-
mainder of the recrystallised material, drain and dry. The
maltosazone is obtained as yellow crystals, m.p. 206°* with
decomposition.

Lactosazone (Phenyl-lactosazone).
C 12 H 20 O 9 (N NHC 6 H 5 ) 2 .
Proceed exactly as for maltosazone. When the heating is
complete, however, remove the boiling-tube from the water-bath,
and allow it to cool spontaneously in the air. (Lactosazone does
not require the extremely slow cooling used for maltosazone in
order to ensure rapid subsequent filtration.) Finally complete
the cooling in cold water, and then filter at the pump, wash with
cold water, and drain thoroughly. (Yield, 2 g.). Lactosazone
is not so soluble as maltosazone in boiling water: for recrystallisa-
tion, therefore, boil a portion of the lactosazone with water, and
then add ethanol drop by drop until a clear solution is obtained.
Allow to cool slowly. Examine the crystals as before, and note
the dense yellow clusters of very fine needles (sometimes referred
to as 1'hedgehog" crystals): compare with Fig. 63(C). Filter
off the remainder of the lactosazone, drain and dry. The pure
lactosazone is obtained as yellow crystals, m.p. 208° with de-
* This is the value originally given by Fischer for the m.p. of maltosazone: it
is a value obtained, however, only if the capillary tube containing the material
is placed in a bath previously heated to about 180° and the temperature then
rapidly increased. The m.p. of most samples of maltosazone, when determined
in the usual way, is 190-192°.
The m.p. of lactosazone used to be given as 200°, but the pure samples of
lactose now available give an osazone having the higher m.p. of 208° given
above. In view of these variations in the m.p., and also of the fact that the
m.p.s of all osazones of the commoner sugars lie very close together, the
identification of an osazone should be based primarily on its crystal form: for
this purpose it is frequently unnecessary to recrystallise the osazone, as the
crystal form can often be observed excellently if a few drops of the original
solution are used.
PREPARATIONS 141
composition, the material darkening in colour immediately before
melting.

a- and £-Pentacetylglucose. C 6 H 7 O(O-COCHg) 5 .


When glucose is heated with an excess of acetic anhydride in the presence
of a catalyst, all five hydroxyl groups are acetylated, and the resulting pen-
tacetyl-glucose can clearly exist in two isomeric forms, corresponding to the a
and p forms of glucose itself (see Formulae I and II, p. 135). When zinc
chloride is used as a catalyst, the a-pentacetylglucose is formed, and when
sodium acetate is used, the [i-pentacetylglucose is produced. It is probable
that the product in each case contains traces of the other isomeride, which
however can be readily eliminated by recrystallisation.

(A) a-PENTACETYLGLUCOSE. Required: Zinc chloride,


ca. i g.; acetic anhydride, 25 ml.; glucose, 5 g.
From a clean, dry stick of zinc chloride, break off a piece
weighing roughly i g., crush it quickly into coarse fragments in
a mortar, and then add it to 25 ml. of acetic anhydride contained
in a ioo ml. round-bottomed or conical flask. (Owing to the
very deliquescent nature of zinc chloride, this manipulation
must be carried out as rapidly as possible: hence have both the
acetic anhydride in the flask, and the mortar available near the
balance, before the zinc chloride stick is withdrawn from the
stock bottle.) Fit the flask with a reflux water-condenser and
heat the mixture of zinc chloride and acetic anhydride on a
vigorously boiling water-bath for about 5 minutes until the
maximum temperature is reached and nearly all the chloride has
dissolved. Now remove the condenser and add 5 g. of pow-
dered glucose (anhydrous or monohydrate) cautiously to the
acetic anhydride, shaking the mixture around occasionally during
the addition, in order to control the vigorous reaction which
follows. Finally replace the condenser and heat the mixture for i
hour on the water-bath, and then pour the liquid into about 250
ml. of cold water. The latter should preferably be cooled exter-
nally with ice-water, and be stirred vigorously during the addition
of the acetylated product. A viscous oil separates at the bottom of
the beaker, and if occasionally stirred will crystallise within about
io minutes. After solidification of the oil, allow the mixture to
stand for a further 15 minutes, and then filter at the pump. If
any large lumps of the crude acetyl compound have formed,
transfer them to a mortar, pulverise, and then wash them back
into the Buchner funnel. Finally wash the product on the filter
thoroughly with water, and drain. (Yield of crude material,
142 PRACTICAL ORGANIC CHEMISTRY
7-5-8-0 g.). Recrystallise the product from rectified spirit
until the y.-pentacetylglucose is obtained as colourless crystals
melting sharply at 110-111°. Two recrystallisations are usually
sufficient for this purpose.
(B) fi-PENTACETYLGLUCOSE. Required: Anhydrous
sodium acetate, 2*5 g.; acetic anhydride, 25 ml.; glucose, 5 g.
Carry out this preparation precisely as described for the a-
compound, but instead of zinc chloride add 2*5 g. of anhy-
drous powdered sodium acetate (preparation, p. 116) to the acetic
anhydride. When this mixture has been heated on the water-
bath for 5 minutes, and the greater part of the acetate has dis-
solved, add the 5 g. of powdered glucose. After heating for
i hour, pour into cold water as before. The viscous oil crystal-
lises more readily than that obtained in the preparation of the
a-compound. Filter the solid material at the pump, breaking up
any lumps as before, wash thoroughly with water and drain.
(Yield of crude product, 10-0-10-5 £•)• Recrystallise from
rectified spirit until the pure ^-pentacetylglucose is obtained
as colourless crystals, m.p. 130-131°: again two recrystallisations
are usually sufficient for this purpose.
Conversion of ^- into a-pentacetylglucose. The p-pentacetyl-
glucose is readily converted into the a-isomeride by heating in acetic
anhydride solution with zinc chloride. Add 0-5 g. of zinc chloride
(rapidly crushed to coarse fragments as before) to 25 ml. of acetic
anhydride and heat on a boiling water-bath for about 5 minutes in
order to dissolve the zinc chloride. Then add 5 g. of pure (3-pent-
acctylglucosc, which will dissolve rapidly in the hot solution. Con-
tinue heating on the water-bath for 30 minutes, and then pour the hot
solution, which will have acquired a pale brown colour, into 250 ml. of
cold water, stirring vigorously. The oily drops rapidly solidify. Filter
the solid product at the pump, wash, drain and recrystallise from
rectified or methylated spirit. One recrystallisation is usually sufficient
to give pure a-pentacetylglucose, m.p. iio-iii°.
For the determination of the number of acetyl groups in pentacetyl-glucose,
see p. 456.

Hexacetyl manni tol.


CH2(O-COCH3)(CH-O COCH3)4CH2(O.COCH3).
Mannitol, CH 1 OH(CHOH) 4 CH 4 OH, is a hexahydric alcohol obtained by the
reduction of mannose. Since ring formation does not occur in mannitol, the
hexacetyl derivative can exist in only one form, and therefore either zinc
chloride or sodium acetate can be used as a catalyst for the acetylation.
PREPARATIONS
Required: Mannitol, 5 g.; acetic anhydride, 30 ml.; zinc
chloride, ca. 0-5 g.
Add 5 g. of finely powdered mannitol to 30 ml. of acetic
anhydride contained in a ioo ml. round-bottomed or conical flask.
Now break off a small fragment (not exceeding 0-5 g.) from a
clean dry stick of zinc chloride, crush it quickly into coarse
fragments in a mortar, and then add it to the acetic anhydride:
this manipulation of the zinc chloride—as in the above preparation
of a-pentacetyl-glucose—should be performed as rapidly as
possible. (Alternatively, 4 g. of powdered anhydrous sodium
acetate may be added in place of the zinc chloride.) Boil the
mixture gently on a sand-bath under a reflux water-condenser for
30 minutes, a clear solution being rapidly obtained. Then pour
the solution into 250 ml. of cold water, stirring the mixture
vigorously for a few minutes until the oil which separates at first
has solidified to a mass of fine colourless crystals. Allow to stand
for 15 minutes, and then filter at the pump, wash thoroughly with
water, and drain. Recrystallise the well-drained material (without
drying) from a small quantity of methylated or rectified spirit,
when the hexacetylmannitol will separate in colourless crystals,
m.p. 120°: yield, 11-5 g. (almost theoretical).
For the determination of the number of acetyl groups in hexacetyl-mannitol,
see p. 456.
a-Methylglucoside. C 6 H 7 O(OH) 4 (OCH 3 ).
When anhydrous glucose is boiled in methanol solution containing a small
quantity of hydrogen chloride, condensation occurs between the meth-
anol and the terminal (uldehydic) hydroxyl
H OCH3 CH3O H group of the glucose molecule, and a mixture
\/ \/ of the isomeric a- and [3-methylglucosides
C- (A and B) is obtained: these correspond to
a- and ^-glucose respectively (compare for-
HCOH HCOH mulae I and II, p. 135).
It should be noted that, since the hydroxyJ
HOCH O HOCH O group concerned in this condensation is
derived from the terminal aldehydic group,
HCOH HCOH the glucosides are similar in chemical nature
to the acetals, e.g., CH 3 CFI(OC 2 Hs) 2 , which
HC- HC - are also formed by the condensation of an
I j aldehyde with an alcohol. Consequently the
CH 2 OH(A) CH 2 OH (B) methylglucosides can be readily hydrolysed
back to methanol and glucose: if, on the other
hand, the remaining hydroxyl groups in the glucose molecule are methylated,
true ethers are obtained and these methyl groups cannot be readily hydrolysed.
H4 PRACTICAL ORGANIC CHEMISTRY
The following preparation works excellently if it is carried out in a
laboratory which has become "inoculated" by the methylglucoside from
previous preparations, or alternatively if some of the glucoside is available
for "seeding" the solution of the crude material; otherwise there may be a
considerable delay before crystallisation starts.

Required: Anhydrous glucose, 20 g.; methanol, 40 ml.


Add 20 g. of pure powdered anhydrous glucose to 40 ml.
of anhydrous methanol (preparation, p. 88) contained in a flask
fitted by means of a rubber stopper to a reflux water-condenser:
close the top of the condenser with a calcium chloride tube.
It is now required to add about 5% of dry hydrogen chloride
to the methanol in the flask. For this purpose, fit a corked
boiling-tube with two narrow delivery-tubes so that it can act
as a wash-bottle: fit the inlet tube to a hydrogen chloride Kipp's
apparatus (p. 104) through a concentrated sulphuric acid wash-
bottle to ensure thorough drying of the gas, and fit the outlet
tube with a calcium chloride tube. Place 2-5 ml. of anhydrous
methanol in the boiling-tube, stand the latter in ice-water, and
bubble hydrogen chloride through the chilled methanol until the
latter is saturated. (The gas should be passed briskly through
the methanol at first, to prevent the latter from *'sucking back"
through the inlet tube.) Then add this saturated methanol with-
out delay to the contents of the flask, and mix well.
Boil the mixture gently on a sand-bath for 4 hours and then de-
cant into a conical flask and cool. Seed the cold solution if neces-
sary with a trace of a-methylglucoside. The glucoside separates as
colourless crystals. When crystallisation ceases, filter the gluco-
side at the pump, drain, wash quickly with a small quantity of
methanol, and then recrystallise from a minimum of methanol.
For this purpose methanol of good quality, but not necessarily
anhydrous, should be used. The ^-methylglucoside is obtained
as colourless crystals, m.p. 165°. Yield, 6-7 g.
If the mother-liquor from the crude product (together with the
washings) is concentrated to nearly half its original volume by
gentle distillation, and is then cooled and seeded with a trace of
the first crop, a second and less pure crop of the a-methylglucoside
is obtained. This should be purified by recrystallisation from
the mother-liquor obtained from the recrystallisation of the first
crop, and then if necessary recrystallised a second time from a
small quantity of fresh methanol. Yield of second crop, about
2'5 g-
The crude concentrated mother-liquor still contains some
PREPARATIONS '45
a-methylglucoside, together with the more soluble (3-methyl-
glucoside: the amount of the latter is too small, however, to
warrant attempted isolation.
If difficulty is experienced in inducing the first crude crop of the a-glucoside
to ciystallise, place a few drops of the solution on a watch-glass and expose
freely to the air, with occasional scratching: meanwhile keep the main volume
of the solution securely corked in the conical flask. After an interval of varying
length (possibly several days), partial crystallisation occurs in the material
on the watch-glass. Then seed the solution with this material: crystallisation
of the first main crop will rapidly follow.
a-Methylglucoside responds to General Tests i and 2 for carbo-
hydrates given on p. 366 (blackening with sulphuric acid, and Molisch's
test). Since, however, the glucoside does not contain a free aldehydic
hydroxyl group, it does not possess the reducing properties of glucose
itself. Confirm this by applying to pure a-methylglucoside Tests i and
2 for glucose (p. 367), i.e.^ the reduction of ammoniacal silver nitrate
and of Fehling's solution respectively. No reduction is obtained in
either case, although prolonged warming in Test i and (in particular)
prolonged boiling in Test 2 causes partial hydrolysis of the gludoside
with consequent slight reduction.
Periodate Oxidation of i,2-Diols.
Sodium metaperiodate (NaIO4) in cold aqueous solution readily oxidises
i,2-diols with splitting of the molecule and the consequent formation of
aldehydes or ketones: thus ethylene glycol gives formaldehyde and pinacol
gives acetone. In the case of a i,2,3-triol, the central carbon atom of the triol
CH 1 (OH)-CH 2 (OH) -> 2CH8O
(CHa)2C(OH) • C(OH)(CH8), -> 2(CHa)1CO
system breaks off as formic acid, whereas the other two are oxidised as before to
aldehydes or ketones, according to the terminal substituents: for example,
glycerol gives two equivalents of formaldehyde and one of formic acid.
CH2(OH)-CH(OH)-CHt(OH) -> 2CH2O + HCOOH
This selective oxidation has proved of great value in the investigation of
sugar structures. For this purpose, a glycoside is frequently employed to protect
CH8O H CH8O H CH8O H CH8O H
\/ \/ \/ \/
___
— i
c>
V ^
.
i
/-«
\_,

CHOH CHO CHOH CHO

CHOH O CHO O CHOH O + HCOOH


O CHO
CH .J CH CHOH I
CH-
CH8OH CH1OH CH-
CH1OH
CH1OH
(I) (U) (III) (IV)
146 PRACTICAL ORGANIC CHEMISTRY
the terminal group. It will be seen that a methyl aldopento-furanoside (I) will
give solely the dialdehyde (II), whereas a methyl aldohexo-pyranose (III) will
give the dialdehyde (IV) and one equivalent of formic acid, which may be
estimated.
In the following examples, pinacol is oxidised to acetone, which is identified as
its semicarbazone and its 2,4-dinitrophenylhydrazone, and glycerol is oxidised to
formaldehyde and formic acid. The formaldehyde is readily detected by the con-
densation product which it gives with "dimedone," 5,5-dimethylcyclohexan-i,3-
dione (p. 277).
For these experiments, prepare two solutions: (A) A solution of
2-5 g. of sodium metaperiodate in 50 mi. of water. A clear solution
can be readily prepared by gentle warming, and then cooled.
(B) A solution of i g. of "dimedone" (preparation, p. 277) in 10 ml.
of ethanol. This solution will be required only for the glycerol oxida-
tion experiment.
OXIDATION OF PINACOL.
Dissolve i g. of pinacol (preparation, p. 148) in 20 ml. of
water, and add 20 ml. of the 5% aqueous sodium periodate
solution. After 15 minutes, distil the clear solution, collecting
the first 5 ml. of distillate. Treat this distillate with 2,4-dinitro-
phenylhydrazine solution A (p. 263). Acetone 2,4-dinitrophenyl-
hydrazone rapidly separates from the solution; when filtered off,
washed with a small quantity of ethanol, and dried, it has m.p.
126-127°, and after recrystallisation from ethanol it has m.p.
128°.
OXIDATION OF GLYCEROL.
Dissolve 0-5 ml. of glycerol in 20 ml. of water, and add 20 ml.
of the above 5% aqueous sodium periodate solution. After
15-20 minutes add 12 ml. of the above 10% ethanolic dimedone
solution, and stir well at intervals for another 15 minutes. The
addition of the dimedone solution may cause a rapid precipitation
of some of the dimedone itself, which is only slightly soluble in
water, whereas the formaldehyde-dimedone compound separates
more slowly from the solution.
Filter the mixed product at the pump, and wash it well with
ethanol to remove excess of dimedone, and then with water
and again with ethanol. The dried white residual "methylene-
dimedone", m.p. 186-188°, weighs 0-55-0-65 g. It may be
recrystallised from ethanol containing about 10% of water, and
then has m.p. 189°.
Selenium Dioxide Oxidations.
Selenium dioxide, SeO2, is very poisonous (cf. p. 147), but is valuable particu-
larly for the oxidation of methylene (:CH 2 ) groups to carbonyl (:CO) groups.
PREPARATIONS 147
This oxidation proceeds readily if the methylene group is activated by linkage to
(a) a carbonyl group, (b) an aromatic ring; (c) an olefine link also activates
adjacent :CH2 and -CH: groups.
Examples. (^z)CH1COCH, -*- CH.COCHO
Also cyclohexanone -> cyclohexan-i,2-dione
(b) 0,H5CH1C4H6 -> C4H8COC4H6
CeHjCH.CH.C.H, -» C.HftCO-COCeH5
(c) CH1CHiCH1 -> CH1COCHO.
Compounds containing olefine links may be oxidised to i,2-diketones, as in
C 4 H^CHiCHC 4 H 5 -* CeHBCO-COCeHR. Anthracene is readily oxidised to
anthraquinone, but phenanthrene is almost unaffected.
In certain cases, selenium dioxide may act solely as a dehydrogenating agent,
as in the examples:
C1H6OOC-CH1-CH1COOC1H5 -* C,H6OOOCH:CH-COOC,H6
Diethyl succinate Diethyl fumarate
CH1COCH1-CH1COCH8 -» CH8COCHrCHCOCH,
Acetonyl-acetone Diacetyl-ethylene
(«-Hexan-2,5-dione) (n-Hex-3-ene-2,s-dione)
The following oxidation of camphor to camphor-quinone illustrates the
oxidising action of selenium dioxide, and readily gives a crystalline product.
CAUTION. The vapour of selenium dioxide is poisonous, and all operations
involving the hot material, alone or in solution, should be performed in a
fume-cupboard. If lumps of selenium dioxide have to be powdered in a mortar,
the latter should also be in a fume-cupboard, with the window lowered as far
as possible, to avoid inhaling the fine dust. (cf. p. 191)
Camphorquinone from Camphor
When camphor (I) is heated with selenium dioxide in acetic acid, the methy-
lene group next to the carbonyl group is oxidised also to a carbonyl group, to
form camphorquinone (II). Note that the compound (II) is not a true quinone
but a i,2-diketone:
CH 3 CH 3 CH3

H2C CH €H 2 H2C CH CO H2C5 CH CH2


(I) (II) (III)
it has the characteristic yellow colour of such diketones, whereas camphor is
colourless. The systematic name of camphorquinone should therefore be
2, 3-dioxocamphane, derived from the parent hydrocarbon camphane (III).
Required: Camphor, 5 g.; selenium dioxide, 6 g.; acetic
anhydride, 5 ml.
148 PRACTICAL ORGANIC CHEMISTRY
In this preparation, the (+) or dextro-rotatory (natural) cam-
phor or the (±) or racemic (synthetic) camphor can be used.
Perform the oxidation in a fume-cupboard.
Place a mixture of 5 g. of camphor, 6 g. of powdered selenium
dioxide and 5 ml. of acetic anhydride in flask fitted with a reflux
water-condenser. Heat the flask in an oil-bath for 3 hours at
140-150° so that gentle boiling occurs: shake the mixture from
time to time.
Then cool the reaction-mixture, filter it at the pump, leaving
a black residue of selenium, and wash out the flask twice with
2 x 5 ml. of acetic acid, passing the washings also through the
filter. Dilute the united filtrates with water, and make the
solution alkaline with 10% aqueous sodium hydroxide, which
precipitates the camphorquinone. Cool, filter off the yellow
camphorquinone at the pump, wash with water and drain
thoroughly.
The camphorquinone can be purified in either of two ways,
(i) To save time, the drained but still damp material can be
recrystallised from water containing 10% of acetic acid, the hot
filtered solution being cooled and vigorously stirred. The
quinone separates as brilliant yellow crystals (yield, 2-5 g.),
m.p. 192-194°, increased to 196-197° by a second recrystal-
lisation. (ii) The crude camphorquinone can be dried in a
vacuum desiccator (weight of dry quinone, 5 g.), and then
recrystallised from petroleum (b.p. 100-120°), the hot solution
being filtered through a fluted paper in a pre-heated funnel.
The quinone separates in beautiful crystals, m.p. 196-197°, 2-8 g.
The m.p. of the quinone obtained from the optically inactive
camphor is almost identical with the above values, obtained from
dextro-camphor.
The melting-points of the dextro and laevo forms of any optically active
compound may, as in this case, be virtually identical with that of the racemic
form: in many compounds however there is a marked difference in melting-
point, and often in solubility, between the (+ ) and ( -) forms on one hand and
the (±) form on the other.

Pinacol. (CH3)8C(OH)-C(OH)(CH8)2. (Reduction of Acetone)


Acetone when treated in ethanol with sodium undergoes reduction mainly
to isopropanol. By modifying the conditions, however, acetone may be induced
to undergo a bimolecular reduction to pinacol.
2(CH,)2CO -* (CHj) 2 C-C(CH 8 ),
OH OH
Aromatic ketones undergo this type of reduction particularly readily.
PREPARATIONS 149
Two methods of preparing pinacol from acteone are given below. In
Method (A) sodium is added to acetone which is floating on 30% aqueous potas-
sium hydroxide and which therefore contains a strictly limited amount of
water. The method is simple and reasonably rapid but gives a low yield of
pinacol. In Method (B), a modified method due to R. Adams, magnesium is
treated with mercuric chloride and thus activated by the formation, of a film of
magnesium amalgam. It therefore reacts with acetone to give the magnesium
derivative of pinacol, which on hydrolysis furnishes the free pinacol. The scale

2(CHJ1CO + Mg -> (CH,)2C- C(CH8), -> (CHJ 2 C -C(CH3),


OH OH

Mg
of this preparation can readily be increased above that given below.

METHOD (A)
Required: Acetone, 60 ml.; 30% aqueous potassium hydroxide,
90 ml.; sodium, 17 g.
Fit a 250 ml. round-bottomed flask with a refhix water-
condenser down which pieces of sodium may be dropped:
alternatively, use a flask having a short straight stoppered side-
arm for this purpose.
Place 90 ml. of 30% aqueous potassium hydroxide and 60 ml.
of acetone in the flask. Weigh out 17 g. of sodium, cut it into
small lumps or strips, and store these in a short wide-necked
corked bottle for protection from the atmosphere. Now add the
sodium, withdrawn one piece at a time with tongs or a pointed
glass rod, to the mixture: the sodium floats on the upper layer
of acetone as it reacts. Occasionally swirl the mixture gently
around, taking great care that the sodium does not come in
contact with the lower solution of potash, otherwise local over-
heating and charring will occur. (If the sodium should stick in
the condenser during the addition, push it down with a glass rod
having at its upper end either a right-angle bend, or a cork firmly
affixed, so that the lower end of the rod can project only just
beyond the bottom of the condenser: if it slips from the fingers,
it cannot therefore smash the base of the flask.)
As the reaction of the pieces of sodium becomes steadily
slower, add water in small quantities from time to time very
cautiously.
When the sodium has completely dissolved, pour the reaction-
mixture into a separating-funnel, run off the strongly alkaline
lower layer, and dry the upper layer over sodium sulphate (not
ISO PRACTICAL ORGANIC CHEMISTRY
calcium chloride). Then fractionally distil the dried liquid up a
short column, and collect the fraction of b.p. 150-180° (mainly at
170-172°).
Work up the product by method (a) or (b): method (b) affords
the anhydrous pinacol.
(a) Cool the fraction of b.p. 150-180° in ice-water, and add
water (ca. 5 ml.) dropwise with stirring. The crystalline hexa-
hydrate of pinacol is formed with considerable heat evolution:
directly the product becomes solid, stop adding water, for an
excess will redissolve the hexahydrate. Transfer the hexahydrate
(yield 10-11 g.) on to a pad consisting of several thicknesses of
drying-paper, and press it with another pad to remove all mois-
ture, transferring the hydrate if necessary to a fresh pad to com-
plete the drying. Then store it in a bottle having a well-fitting
stopper. The sample may be recrystallised from water (ca. io ml.)
before drying: yield of pure hexahydrate, 9 g.
(b) Add about 60 ml. of petroleum (b.p. 60-80°) with stirring
to the fraction of b.p. 150-180°, thus precipitating the pure
anhydrous pinacol (2-5-3 ?•)• Filter tn*s °ff> and then shake the
filtrate with ca. 4 ml. of water: the remaining pinacol now
separates as the hexahydrate (5 g.). The two crops may be
united and recrystallised from ca. io ml. of water (total yield of
hexahydrate, 8-9 g.). Dry and bottle the product rapidly as
described in (a).
The anhydrous white crystalline pinacol has m.p. 42°, b.p.
172°, and has a strong odour of camphor: the hexahydrate has
m.p. 46°.
Both forms sublime very readily, even at room temperature: a small
sample on exposure to the air will completely volatilise in a short time,
particularly on a warm day or if the sample is exposed to a gentle current
of air. Hence the above method for rapid drying. A sample confined in
an atmospheric desiccator over calcium chloride rapidly disappears as
the vapour is adsorbed by the calcium chloride. A sample of the hexa-
hydrate similarly confined over sodium hydroxide undergoes steady
dehydration with initial liquefaction, for the m.p. of the hydrated-
anhydrous mixture is below room temperature: as the dehydration
proceeds to completion, complete resolidification occurs.

METHOD (B)
Required: Magnesium, 8-0 g.; mercuric chloride, 9*0 g.; dry
benzene, 150 ml.; dry acetone, 75 ml.
The acetone employed should be dried over calcium chloride
for 2-3 days before use. The benzene should be similarly dried
PREPARATIONS 151
although a shorter period is sufficient. The apparatus must also
be thoroughly dry.
Fit a 500 ml. round-bottomed flask with a dropping-funnel,
and with an efficient reflux water-condenser having a calcium
chloride guard-tube at the top.
Place 8-0 g. of magnesium turnings or ribbon and 80 ml. of
the dry benzene in the flask. Prepare a solution of 9-0 g. of
mercuric chloride in 50 ml. of the dry acetone, transfer it to the
dropping-funnel, and then allow it to enter the flask slowly at
first, and then more rapidly, so that the addition takes about
3-5 minutes. The reaction usually starts shortly after the initial
addition of the mercuric chloride solution: if it is delayed, it
may then start vigorously, and the flask may have to be cooled
in water to prevent escape of acetone through the condenser.
As the reaction beings to subside, run in from the dropping-
funnel without delay a mixture of 25 ml. of acetone and 20 ml.
of benzene, in order to maintain a brisk and continuous reaction.
When the reaction finally subsides, heat the mixture on a boiling
water-bath for 45 minutes with occasional shaking. If the shak-
ing does not break up the spongy mass of magnesium pinacolate,
cool the flask at the end of this period, remove it from the
condenser, and then cork and shake it vigorously to disintegrate
the reaction product. Replace the condenser and heat the
mixture for a further 30 minutes.
Now add 20 ml. of water from the funnel and continue heating
for 30 minutes, with occasional shaking. Then allow the mixture
to cool to about 50°, and filter it at the pump. Return the
collected solid to the flask, add 50 ml. of benzene, and heat as
before for 10 minutes to extract any remaining pinacol, and
again filter. Unite the filtrates and concentrate them by distil-
lation to about half the original volume in order to remove any
unchanged acetone. Add 30 ml. of water to the concentrated
benzene solution, and cool the stirred mixture to 10-12°. After
10 minutes, filter off the pinacol hydrate at the pump, wash it
with a small quantity of benzene, and after draining, recrystallise
it from water, adding charcoal if the crude pinacol hydrate was
discoloured. Yield of pinacol hydrate, 35 g.
The pinacol hydrate may be used (i) for conversion to pina-
colone (see below), and (ii) to illustrate the oxidation of i,2-diols
to aldehydes or ketones by periodic acid (p. 145).
Tetraphenylethylene Glycol. This preparation illustrates the mild con-
ditions under which aryl ketones may undergo bimolecular reduction to com-
152 PRACTICAL ORGANIC CHEMISTRY
pounds of the pinacol type.
Dissolve i g. of powdered benzophenone in 6-7 ml. of cold isopropanol with
shaking, add i drop of glacial acetic acid, and then confine the solution either
in a glass receiver having a ground-glass stopper, or in a tube which is sealed
2(C6H^)1CO -> (C6H6)tC(OH)-C(OH) (C«H5),
or closed with a tightly fitting rubber bung. Place the container on a window-
ledge in full daylight and (if possible!) in sunlight. Within a few days in
summer (and 2-3 weeks in winter), crystals of tetraphenylethylene glycol
separate. Filter these off, and recrystallise from ethanol. M. p. 189°.

Pinacolone. (CH8)3C'COCH3 The Pinacol-Pinacolone


Rearrangement.
When pinacol is warmed with acids, it undergoes rearrangement to pina-
colone, with an over-all loss of one molecule of water.
This rearrangement is general for i,2-diols of the type R 2 C(OH)-C(OH)-R 2
where the groups R may be alike or different, and may be alkyl or aryl groups.
R R R R R

R-C - C-R - R— C— — C— R -> R-C -- C-R -> R-C -- C-R


I l I l I IN I o
HO + OH R OH R O— H R
H
(I) (II) (HI) (IV)
The probable mechanism of this change is first proton addition to one oxygen
atom of the pinacol to give (I), which loses water to give the carbonium ion (II).
The group R then migrates to give the isomeric ion (III), which loses a proton,
giving the pinacolone (IV).
Required: Pinacol hexahydrate, 10 g.; concentrated sulphuric
acid, 15 ml. (28 g.).
Add cautiously 15 ml. of concentrated sulphuric acid to 50 ml.
of water in a ioo ml. distilling-flask, and then add 10 g. of pinacol
hydrate. Distil the solution slowly. When about 40 ml. of
distillate (consisting of pinacolone and water) have been collected,
and no more pinacolone comes over, extract the distillate with
ether. Dry the extract over sodium sulphate. Distil the dry
filtered extract carefully, with the normal precautions for ether
distillation (p. 164). When the ether has been removed, continue
the distillation slowly, rejecting any fraction coming over below
100°. Collect the pinacolone, b.p. 106°, as a colourless liquid
having a peppermint odour. Yield, 4-5-5-0 g. A small quantity
of higher-boiling material remains in the flask.
Benzhydrol (Diphenylcarbinol), (C«H6)2CH-OH, from Benzo-
phenone. The Meerwein-Ponndorf-Verley Reductions.
When aldehydes or ketones are heated with an excess of isopropanol in the
PREPARATIONS 153
presence of aluminium isopropoxidc, Al • [OCH(CH 3 ) 2 ] 3 , the overall reaction
may be represented as a reduction of the carbonyl group of the aldehyde or
ketone, with oxidation of the isopropanol to acetone:

R-CHO + HO-CH(CH8), -> RCH 2 OH + OC(CH3)2


R 2 CO + HO-CH(CH8), -* R2CHOH + OC(CH3),
In view of the boiling-points of acetone (57°) and isopropanol (82°), the
acetone can be steadily distilled off from the reaction-mixture, and the reduction
ultimately becomes virtually complete.
This type of reduction has the advantage of requiring only mild conditions,
and also of leaving unaffected various groups such as olefine groups, nitro groups,
and halogen atoms in aliphatic compounds, which might be affected by other
more vigorous reagents. For example, brornal under the above conditions gives
tribromoethanol (or avertin): CBr3-CHO -»• CBr 3 -CH 2 OH. The immunity
of olefine groups has made this type of reduction of particular value in steroid
investigations.
In the following preparation to illustrate the Meerwein-Ponndorf-Verley reduc-
tion, a solution of benzophenone in isopropanol is rapidly reduced in the presence
of aluminium isopropoxide to benzhydrol: (C 6 H^) 2 CO -> (C a H 6 ) 2 CH-OH. It
is clear that the aluminium isopropoxide must take some essential part in this
reaction, for benzophenone when dissolved even in cold isopropanol with a trace
of acetic acid is reduced to tetraphenylethyleneglycol (p. 150).
The mechanism of the reduction remains uncertain. The work of E. D.
Williams, K. A. Krieger and A. R. Day (1953)* using deuterium-labelled
aluminium isopropoxide, shows that hydrogen atoms are transferred predomi-
nantly from the central carbon atom of an isopropoxide group to the carbon
atom of the carbonyl group undergoing reduction, the process probably involving
a cyclic complex:
Me 2 Me2 Me 2
C C C
/ \ S \ S
O H ^=T O H ^±f O H ^> H
I i i I l
(Me 2 CHO) 2 Al CR 2 (Me 2 CHO) 2 Al CR 2 (Me 2 CHO) 2 Al CR 2 HOCR 2
// \!l \/
O O O
Aluminium isopropoxide can be obtained as a fine powder from technical
sources. When the bottle has once been opened however, the stopper should
be firmly replaced and covered with wax: more conveniently, the stoppered
bottle can be kept in an atmospheric desiccator over calcium chloride or sodium
hydroxide, preferably in the dark.
It is advisable in any case before an experiment to place the weighed alumin-
ium isopropoxide overnight in a shallow dish in a vacuum desiccator over sodium
hydroxide. The isopropanol should be dried over anhydrous sodium sulphate,
and the clear liquid decanted off before use.

* J. Amer. Chem. Soc., 75, 2404 (1953)-


154 PRACTICAL ORGANIC CHEMISTRY
Required: Benzophenone, 2 g.; aluminium isopropoxide, 2-5 g.;
isopropanol, 20 ml.
The powdered isopropoxide and the isopropanol must be dried as
described above.
This experiment requires a 50 ml. flask attached by a ground-
glass neck or a rubber bung (not a cork) to an efficient fraction-
ating column. This may be of the type shown in Fig. U(B)
(p. 26) with at least 4 inches of column packed with glass rings,
and without external lagging: or a less efficient type of column,
for example, one similar to that shown in the micro-model,
Fig. 39 (p. 64), in which the column is 6-8 inches high. A
water-condenser is fitted to the column.
Place in the flask 2 g. of benzophenone, 15 ml. of isopropanol
and 2-5 g. of aluminium isopropoxide. This mixture has now
to be heated gently under reflux so that the temperature regis-
tered by the thermometer in the column does not exceed 80°,
i.e., so that only acetone distils. For this purpose, the flask
should preferably be heated in an oil-bath: direct heating, even
over an asbestos sheet, may cause local overheating and decompo-
sition; the use of a water-bath on the other hand may make the
column undesirably damp.
Adjust the temperature so that acetone distils very slowly. After
about i hour the distillation should be complete: confirm by
testing a drop of the distillate with 2,4-dinitrophenylhydrazine
solution. Now add an extra 5 ml. of isopropanol, and continue
the slow distillation until the boiling-point of the distillate reaches
82°, i.e., until isopropanol begins to distil: continue the distilla-
tion until the distillate gives a negative reaction for acetone.
(Total time of distillation is about i£ hours.)
Disconnect the column, and remove the flask from the oil-
bath. Add 25 ml. of dilute hydrochloric acid to the flask, shake
the contents vigorously, and chill in ice-water, when crystals of
benzhydrol will separate. (Occasionally the hydrol will separate
initially as an oil, which crystallises on vigorous stirring.)
Filter the crystals at the pump, wash them with water, and
drain well. To save time, the product may be recrystallised
directly from an ethanol-water mixture (1:2 by vol.), and
obtained as colourless crystals, m.p. 68°. Alternatively, the
crude product can be dried in a desiccator (yield of dry product,
1-9-2-0 g., m.p. 65-67°) and recrystallised from petroleum
(b.p. 60-80°), and obtained as needles, m.p. 68°.
PREPARATIONS 155
Lithium Aluminium Hydride Reductions.
Lithium aluminium hydride, LiAlH 4 , is a very active reducing agent, and is
used particularly for the ready reduction of carboxylic acids (or their esters)
to primary alcohols: R-COOH -> R-CH8OH.
It will also reduce acid chlorides, acid anhydrides and aldehydes to primary
alcohols, ketones to secondary alcohols, and amides to the corresponding
amines: R-CONH 8 -»• R-CH 8 NH 2 . Nitro-hydrocarbons if aromatic are
usually reduced to azo-compounds, and if aliphatic to primary amines. The
C:C bond in aliphatic compounds is usually unaffected, but in aromatic com-
pounds the bond may be hydrogenated if it is directly linked to the aromatic
nucleus: thus cinnamic acid gives 3-phenylpropan-i-ol: C 6 H 6 CH:CH-COOH
-^C6H6CH2CH2CH8OH. The C:.C bond, unless strongly activated by neigh-
bouring groups, is also usually unaffected.
Lithium aluminium hydride if carelessly manipulated may be dangerous for
two distinct reasons. The material is caustic, and should not be allowed to
touch the skin: it is particularly important that the finely divided material
should be kept away from the lips, nostrils and eyes, and consequently pulver-
isation in a mortar must be carried out with the mortar in a fume-cupboard,
and with the window drawn down as far as possible in front of the operator.
This danger from handling has however been greatly reduced, for the hydride
is now sold in stated amounts as a coarse powder enclosed in a polythene bag
in a metal container: this powder dissolves readily in ether, and preliminary
pulverisation is unnecessary.
The second danger may arise from the careless treatment of the hydride in
a glass vessel with water or acid: a significant volume of hydrogen may be
evolved, and a fragment of the hydride may ignite and so cause an explosion.
These conditions should never arise in the course of careful work.
In an experiment, a slight excess of the hydride is employed to ensure the
complete reduction: the unused hydride must then be destroyed. This can be
done by the cautious addition of (a) water, or (6) ordinary undried ether, which
will ensure that the supply of water is both small and gradual, or (<:) an ester
such as ethyl acetate, \shich will be reduced to ethanol. The first of these
methods, namely the addition of water, is hazardous and should be avoided.
In the following experiment, salicylic acid is reduced to o-hydroxybenzyl
alcohol (or saligenin), which being crystalline is readily isolated: the excess of
hydride is destroyed by the addition of undried ether, and the aluminium
hydroxide then brought into solution by the addition of sulphuric acid.
o-Hydroxybenzyl Alcohol (Saligenin) C6H4(OH)-CH2OH from
Salicylic Acid.
The student should read the above directions for the safe manipu-
lation of the hydride before starting this experiment.
Required: Salicylic acid, 6-0 g.; lithium aluminium hydride,
2-5 g.; dry ether, 165 ml.
Assemble in a fume-cupboard a 3-necked flask fitted with a
stirrer, a reflux condenser, and a dropping-funnel, the apparatus
156 PRACTICAL ORGANIC CHEMISTRY
being thoroughly dry, and the condenser and funnel closed by
calcium chloride tubes (Fig. 23(0), p. 46).
Run 90 ml. of dry ether into the flask and start the stirring.
Weigh out 2-5 g. of lithium aluminium hydride, and then
divide 0*5 g. of this amount into very small portions: add these
portions in turn cautiously to the stirred ether to remove any
traces of water which in spite of the above precautions may be
present in the reaction flask. Then add the remaining 2-0 g. of
the hydride more rapidly. When the addition is complete,
continue stirring the mixture for 15 minutes; the hydride should
dissolve in the ether except for a slight grey suspension. (If at
the end of this period the larger particles of the hydride have not
disintegrated, boil the stirred mixture under reflux on a water-
bath for a further 15 minutes.)
Now cool the mixture thoroughly in ice-water, and run in
over a period of 45 minutes a solution of 6-0 g. of dry salicylic
acid in 75 ml. of dry ether. When the addition of the acid to the
stirred solution is complete, heat the mixture under reflux on
the water-bath for 15 minutes to ensure completion of the
reduction. Then thoroughly chill the mixture in ice-water, and
hydrolyse any unused hydride by the slow addition of 50 ml.
of ordinary undried ether, followed similarly by 75 ml. of dilute
sulphuric acid.
Transfer the reaction-mixture to a separating-funnel, run off
the aqueous layer, and collect the ethereal layer. Extract the
aqueous layer twice with ether (2 x 25 ml.), add the extracts
to the main ethereal solution and dry over sodium sulphate.
Distil the filtered ethereal solution, using a ioo ml. flask
fitted with a dropping-funnel and a side-arm for the condenser:
observe all the normal precautions for ether distillation (p. 162)
and run the ethereal solution into the flask as fast as the ether
distils over. When all the ether has distilled off, detach and cool
the flask, when the oily colourless residue of saligenin will
rapidly crystallise. Weight of product, 5-0 g.; m.p. 75-82°.
Recrystallise either from a mixture of benzene and petroleum
(b.p. 60-80°), or from a minimum of water, allowing the stirred
aqueous solution to cool to 65-70° before chilling. The dry
crystalline saligenin has m.p. 85-86°.
Saligenin readily sublimes when heated above its m.p., and
consequently cannot be distilled.
Nitration.
One of the chief differences between aliphatic and aromatic hydrocarbons
PREPARATIONS 157
is that the latter when treated with nitric acid (in the presence of sulphuric acid)
undergo direct nitration, benzene being thus converted to nitrobenzene:
C 6 H 5 H + HONO2 ^- C 6 H 5 NO 2 + H2O.

A similar reaction occurs only very rarely with aliphatic hydrocarbons.


It is found experimentally, however, that if benzene is treated with concen-
trated nitric acid alone, the yield of nitrobenzene is small. If, however, the nitric
acid is first mixed with concentrated sulphuric acid, a high yield of nitrobenzene
results.
Ingold and co-workers have shown that nitration is caused by the nitronium
+ + +
ion, NO 2 . The overall reaction is: C 6 H 6 -f- NO 2 > C 6 H 5 NO 2 + H
+
It is considered that the NO1 ion is produced in the mixture of nitric and
sulphuric acids by changes such as:
+
H 8 SO 4 + HNO 3 + HSO4 + H 2 NO 3
+ _ + +
H1NO8 + H 2 SO 4 > HSO 4 + H 8 O 4- NO1

Nitrobenzene. C6H5NO2.
Required: Nitric acid, 35 ml.; sulphuric acid, 40 ml.; benzene,
29 ml. (25 g.).
The conversion of benzene to nitrobenzene has to be performed
with care in order to avoid the further nitration of the nitro-
benzene to m-dinitrobenzene. Place 35 ml. of concentrated nitric
acid in a 500 ml. flask, and add slowly 40 ml. (74 g.) of concen-
trated sulphuric acid, keeping the mixture cool during the addi-
tion by immersing the flask in cold water. Place a thermometer
in this nitrating mixture, and then add very slowly 29 ml. (25 g.)
of benzene. The benzene should be added about 3 ml. at a time,
and the contents of the flask thoroughly mixed after each addition:
the temperature of the mixture must not be allowed to rise above
50°, and should be kept under control if necessary by cooling the
flask in cold water. When all the benzene has been added, fit a
reflux water-condenser to the flask, and place the latter in a
water-bath, which is then maintained at 6o° for 45 minutes.
During this period the flask should be withdrawn from the bath
from time to time and vigorously shaken in order to break up the
nitrobenzene layer which would otherwise float on the dense acid
layer below.
After the 45 minutes' heating, pour the contents of the flask
into a large excess of cold water (about 300 ml.), in which the
nitrobenzene, being heavier than water, sinks to the bottom. Stir
the mixture vigorously in order to wash out as much acid as
IS8 PRACTICAL ORGANIC CHEMISTRY
possible from the nitrobenzene. Decant off as much as possible
of the supernatant aqueous layer,* and then transfer the residual
liquid to a separating-funnel. Run off the lower layer of nitro-
benzene, rejecting the upper aqueous layer, and then return the
nitrobenzene to the separating-funnel, and shake it vigorously
with an equal volume of cold water. Allow the nitrobenzene to
separate again, and then run it off and repeat the washing using
dilute sodium carbonate solution. The nitrobenzene should be
shaken with increasing quantities of the carbonate solution until
the cessation of evolution of carbon dioxide shows that all free
acid has been neutralised.
The nitrobenzene ought now to be separated and again washed
with water to remove traces of sodium carbonate solution: wash-
ing with water at this stage, however, frequently gives an emul-
sion of nitrobenzene and water and takes a very long time to
separate again into two well-defined layers. It is best therefore
to omit this final washing with water, and to separate the nitro-
benzene as completely as possible from the sodium carbonate
solution. Then transfer the nitrobenzene to a small flask, add
some granular calcium chloride, and shake the mixture occasion-
ally until the liquid is quite clear (usually about 20 minutes).
Filter the nitrobenzene through a small fluted filter-paper directly
into a 60 ml. distilling-flask fitted to an air-condenser. Distil the
nitrobenzene carefully, collecting the fraction which boils be-
tween 207° and 211°. Yield, 35 g.
Nitrobenzene is a pale yellow liquid, having a b.p. 210°, and
d, i-20. It has an odour which is similar to that of almonds, and
which is therefore often confused with that of benzaldehyde.
Nitrobenzene is used chiefly for the preparation of aniline.
Nitrobenzene. (Semi-micro scale), (i/io of above scale.)
Place 3-5 ml. of cone. HNO 8 in a 50 ml. round-bottomed flask and add slowly
with cooling 4 ml. of cone. H 2 SO 4 . (Measure the acids from a burette or 5 ml.
measuring cylinder.) Add slowly from a burette 2-9 ml. of benzene, shaking the
mixture well during the addition: the temperature must be kept at 45-50°. Fit
a small reflux water-condenser to the flask and heat in a water-bath maintained
at 60° for 10 minutes. During this period, shake the flask vigorously from time
to time, and then pour the mixture into 30 ml. of cold water. (If emulsification
occurs, add about 5 ml. of chloroform to extract the nitrobenzene.) Proceed as in
the larger-scale experiment above as far as the drying stage. Use only 2-3
small pieces of granular calcium chloride, and dry for 10 minutes. If a clear
liquid is obtained, omit the filtration, and decant carefully into the flask shown
* This is done so that a small separating-funnel of about ioo ml. capacity
may be used for the subsequent washing of the nitrobenzene.
PREPARATIONS 159
in Fig. 36 (p. 63). Distil without water in the condenser (after removal of chloro-
form). Keep the hot vapour of the nitrobenzene around the bulb of the thermo-
meter (which has a considerable heat-capacity) for one minute without actually
distilling, so that the true temperature can be recorded, and then collect the
fraction of b.p. 207-211°. Yield, 2.7 g.
For reactions of nitrobenzene, see pp. 384, 385.

Aromatic Substitution.
The student when preparing disubstituted benzenes should bear in mind
Vorlander's Rules of aromatic substitution, which form the most convenient
modification of Crum Brown's earlier rules. Vorlander stated that if a substance
C»;H r) Q be converted into a substance C 0 H 4 QR, where Q and R are any sub-
stituents, then
(1) The nature of C 6 H 4 QR depends solely on Q, and is independent of R.
(2) The product C«H 4 QR is either
(a) the meta isomeride,
or (b) a mixture of the ortho and para isomerides.
(3) If the group Q contains a double or triple bond, then C 6 H 4 QR will be
the meta isomeride: otherwise, C^H 4 QR will be a mixture of ortho
and para isomerides.
The chief meta directing groups are therefore:
-CHO, -COOH, -CONH 2 , -CN, -NO 8 , -SO 3 H,
and the chief ortho and para directing groups are:
-Cl, -Br,-I, -OH, -OCH8, -NH 8 , -CH, and other alkyl groups.
It must be emphasised that the above are empirical rules, and not scientific
laws, and are not always accurate. The only common exceptions are the
-NHCOCH 3 group, which, like the parent -NH 2 group, directs ortho and
para, the — CHiCHCOOH group (as in cinnamic acid) which also directs ortho
and para, and the - CCl3 group, which directs meta. Moreover, many reactions
which give the meta isomeride (e.g., ?«-dinitrobenzene, p. i6i)aho give traces of
the ortho and para isomerides, and vice-versa.
It is also to be noted that ortho and para substitution often occur together
in the same molecule, so that the group R enters the para and also both the
ortho positions: thus both aniline and phenol on bromination readily give
symmetric (2,4,6) tribromo-compounds (p. 165), while both toluene and phenol
on nitration readily give the symmetric trinitro-derivatives (p. 170).
The course of aromatic substitution has been placed on a more scientific
basis by the following rules of Hammick and Illingworth (Jour. Chem. Soc.,
!93O> 2358). If a monosubstituted benzene derivative has the formula C 6 H 5 XY,
where X is the atom joined to the benzene ring and Y is an atom or group of
atoms attached to X, then:—
XY is meta directing:
(a] if Y is in a higher group in the Periodic Classification than X,
(b) if Y is in the same group as X, but is of lower atomic weight.
XY is ortho and para directing:
i6o PRACTICAL ORGANIC CHEMISTRY
(c) if Y is in a lower group than X,
(d) if X and Y are atoms of the same element,
(e) if the group XY consists of i atom alone.
To apply those rules, only the elements given in the accompanying Table
need usually be considered. Hydrogen is
Group I IV V VI VII considered as being in Group I: if Y consists
H C N O F solely o f hydrogen atoms, t h e latter obey t h e
S Cl above rule; if, however, Y consists partly of
Br hydrogen and partly of another element, both
I attached to X (as in - CHO), then the influence
of the hydrogen can usually be ignored and
the rules applied to the remaining element alone.
Examples of the above classes are:
Meta directing:
(a) -CHO, -COOH, -CN, -CCl 3 , -NO 2 .
(6) -SO2OH.
Ortho and para directing:
(c) -CH 3 , -OH, -OCH3, -NH,, -NHCOCH 3 , -SCN.
(d) -CH 8 -CH 3 (X and Y being the C'C atoms).
-CHrCHCOOH (X and Y being the C:C atoms).
-N:N - (X and Y being the N:N atoms).
M -Cl, -Br, -I.
The student should remember that para compounds have almost invariably
higher melting-points than the corresponding ortho and meta isomerides, as the
following examples show:
Melting-points of Disubstitilted Benzenes
Ortho Meta Para
Dichloro-benzene C 6 H 4 Cl 2 -17 -25 53
Chloro-bromo-benzene C fl H 4 ClBr 12 -21 67
Dibromo-benzene C 6 H 4 Br 2 6 -7 89
Chloro-aniline C 6 H 4 ClNH 2 -2 -10 70
Bromo-aniline C 6 H 4 BrNH 3 31 18 66
Nitro-aniline C 6 H 4 (NO 2 )NH 2 72 114 148
Bromo-phenol C 6 H 4 Br(OH) 5 32 63
Nitro-phenol C 6 H 4 (NO 2 )OH 46 97 114
Bromo-toluene C 6 H 4 BrCH 3 -26 -40 28
Nitro-toluene C 6 H 4 (CH 3 )NO 2 -4 16 52
Toluene sulphonylchloride C 6 H 4 (CH 3 )SO 2 Cl 10 12 66
It will be seen that the para compound is frequently the only isomeride
which is solid at room temperature, a fact which should be borne in mind when
identifying organic compounds.

m-Dinitrobenzene. C6H4(NO2).,.
Required: Fuming nitric acid, 15 ml.; sulphuric acid, 20 ml.;
nitrobenzene, 12 ml.
PREPARATIONS 161
This preparation must be performed in a fume-cupboard,
because nitrous fumes are evolved during the nitration. A
ground-glass flask and air condenser (Fig. 22(A) and (c), p. 43)
should preferably be used.
Place 15 ml. of fuming nitric acid (a1, 1-5) in a 150 ml. flask and
add carefully with shaking 20 ml. (37 g.) of concentrated sul-
phuric acid and then some fragments of unglazed porcelain. Fit a
reflux air-condenser securely to the flask, and then add slowly
down the condenser 12 ml. (14-5 g.) of nitrobenzene: do not
add more than 3 ml. of the nitrobenzene at a time, and after each
addition shake the flask to ensure thorough mixing of the contents.
Now heat the flask on a boiling water-bath for i hour, both the
flask and the condenser being securely clamped in position if
joined by a cork, which the acid fumes evolved may attack and
weaken. Shake the flask vigorously from time to time throughout
this period of heating. Finally pour the mixture carefully with
stirring into an excess of cold water (about 300 ml.), whereupon
the heavy oily dinitrobenzene will rapidly solidify. Filter the
crystalline material at the pump, wash thoroughly with water to
remove all acid, and then drain as completely as possible.
To purify the crude dinitrobenzene, transfer it to a 200 ml.
conical flask fitted with a reflux water-condenser, add about
ioo ml. of rectified spirit, and heat on a water-bath until the
crystalline material dissolves completely. If the solution so
obtained is not quite clear, filter it through a fluted filter-paper
in a heated funnel or a Buchner funnel which has been pre-
heated by the filtration of some boiling solvent. The solution on
cooling deposits m-dinitrobenzene as colourless crystals: yield,
14-15 g. A second recrystallisation is, however, usually necessary
in order to eliminate traces of o- and p-dinitrobenzene, and thus
obtain pure m-dinitrobenzene, m.p. 90°.
For reactions of m-dinitrobenzene, see p. 384» 3^5-
Aniline. C6H5NH2.
Both aliphatic and aromatic nitro-compounds can be readily reduced in acid
solution to the corresponding primary amine. Thus when a mixture of nitro-
benzene and tin is treated with hydrochloric acid, the tin dissolves to give
stannous chloride, SnCl8, which in these circumstances then reacts with more
acid to give stannic chloride, SnCl4, and the nascent hydrogen produced from
Sn + 2HCl = SnCl, + aH SnCl8 + 2HCl = SnCl4 + 2H
C 6 H 6 NO, + 6H = C 6 H 8 NH, + 2H,O
these sources reduces the nitrobenzene to aniline. The stannic chloride com-
bines with the excess of hydrochloric acid to give the complex chlorostannic acid,
162 PRACTICAL ORGANIC CHEMISTRY
H1SnCl6, with which the aniline forms a salt, aniline chlorostannate
(C 4 H 6 NH 1 )J 1 HjSnCU, similar in type to aniline chloroplatinate (p. 448). The
crude product is therefore made strongly alkaline with sodium hydroxide, which
liberates the base with the formation of sodium stannate, and the aniline can
(CeH 6 NHj) 8 H 8 SnCl 5 + 8NaOH = 2C 6 H 5 NH 1 + NaxSnO, +6NaCl + sH 2 O
then be removed by steam-distillation.
Required: Nitrobenzene, 21 ml.; tin, 50 g.; hydrochloric
acid, ioo ml.; sodium hydroxide, 75 g.; common salt, ca. 30 g.
Place 21 ml. (25 g.) of nitrobenzene and 50 g. of granulated
tin in a 600 ml. bolt-head flask fitted with a reflux water-con-
denser. Now pour about 20 ml. of concentrated hydrochloric
acid down the condenser, and shake the contents of the flask
steadily. If the heat of the reaction causes the mixture to boil
too vigorously, moderate the action by immersing the flask
temporarily in cold water. Then as the reaction slackens, pour
another 20 ml. of hydrochloric acid down the condenser, and
shake the flask to ensure good mixing, again cooling the flask if
the action becomes too violent. Continue in this way -until a
total of ioo ml. of hydrochloric acid has been added. Then
heat the flask on a briskly boiling water-bath for 20 minutes. By
these means the reduction is completed by the stannous chloride
present: at the end of this time, therefore, the odour of the nitro-
benzene should be barely perceptible. Now cool the flask in
water, and slowly add a solution of 75 g. of sodium hydroxide
in ioo ml. of water, thus making the solution strongly alkaline
and liberating the aniline. Equip the flask for steam-distillation
as shown in Fig. 15, p. 33, and steam-distil the mixture until
about 175 ml. of distillate have been collected. The aniline is only
moderately soluble in cold water (giving an approximately 3 %
solution), and the greater part therefore separates as oily drops in
the aqueous distillate: in order to reduce further the solubility of
the aniline in the water, add about 30 g. of powdered salt to the
entire distillate and shake thoroughly until all the salt has dis-
solved. In spite of the decreased solubility of the aniline in the
aqueous distillate, an ether extraction is still advisable to ensure
efficient isolation of the aniline. Therefore transfer the distillate
to a separating-funnel,* add about 40 ml. of ether, and shake
vigorously, occasionally relieving the pressure of the ether vapour
within the funnel by momentarily lifting the stopper. Allow the
• If only ioo ml. separating-funnels are available, the distillate must be
divided into two portions and each extracted with ether as described, the final
ether extracts being united for drying with potassium hydroxide.
PREPARATIONS 163
two layers to separate, and then run off the lower aqueous layer,
finally pouring off the remaining ethereal layer through the mouth
of the funnel (to avoid contamination with adherent drops of the
aqueous layer) into a 200 ml. conical flask. Replace the aqueous
solution in the funnel, and again extract with a further 40 ml. of
ether. Proceed as before, and transfer the ethereal layer to the
conical flask. Now add some coarsely powdered potassium
hydroxide to the combined ethereal extracts, and allow the
securely corked flask to stand (preferably overnight) until the
ethereal solution is clear and dry.
Owing to the volatility of ether, and the explosive inflammability
of its vapour when mixed with air, special precautions must be
taken when distilling off this solvent. Fit up the apparatus as
shown in Fig. 64 (or in Fig. 23 (E), p. 45). A is a 6o ml. distilling-
flask fitted with a dropping-funnel B, so that the bottom of the
stem of the funnel passes well below the side-arm of the flask. The
latter is then connected to a water-condenser C, through which an
ample supply of water can be passed. The lower end of C is then
securely fitted into a Buchner flask D of about 300 ml. capacity.
A long piece of rubber tubing is attached to the side-arm of D as
shown, so that the rubber tubing reaches well below the level of
the bench: should any of the heavy ether vapour escape con-
densation during distillation, it will thus be carried away well
below the apparatus. Place some fragments of unglazed porcelain
in A, and extinguish all flames near the apparatus. Now decant
A

FIG. 64.
164 PRACTICAL ORGANIC CHEMISTRY
the dried ethereal solution carefully into a small fluted filter-paper,
so that it filters directly into the funnel B. It is probable that
the water extracted from the ether during drying will have
dissolved some of the potassium hydroxide, and that a mixture of
solid potash and saturated aqueous potash solution will have col-
lected at the bottom of the ether. If some of this aqueous potash
solution should pass into the filter during the decantation of the
ether, it will not pass through the filter-paper whilst the latter is
saturated with the non-miscible ether, but will merely collect at the
bottom of the fluted paper.
When the filtration is complete, run about 25 ml. of the ether
solution into A, and place under the latter a water-bath which
has been brought to the boil at some considerable distance from
the apparatus. (With large classes, or in crowded laboratories,
the water-baths may well be heated in fume-cupboards, which
are usually at a safe distance for this purpose from the working
benches.) As the ether distils off from A, run in more of the
solution from B, and thus continue until it appears that all the
ether has been distilled off, and only aniline remains in A. To
complete the latter stages of the distillation, it may be necessary
to reheat the water-bath: this should be done as before at a safe
distance from the apparatus. Now detach the Buchner flask D,
pour the contents into an ether residue bottle, and then replace
C by an air-condenser: finally replace the funnel B by a thermo-
meter reading to at least 200°. Distil the residual aniline carefully
by direct heating over a gauze, and collect the fraction boiling at
180-185°. During the early part of distillation, a small quantity
of ether may come over although the recorded temperature may
be well above its boiling-point: hence ensure that the flame is
kept well away from the open end of the condenser. Yield, 17 g.
Aniline when freshly distilled is a colourless liquid of b.p. 184°
and d, 1-025: on exposure to air and light, it develops a deep
brown colour. It is an extremely important substance techni-
cally, being the starting point of many azo and other dyes.
Aniline. (Semi-micro Scale), (i/io of above scale.)
Place 2*1 ml. (measured from a micro-burette) of nitro-benzene and 5 g.
of granulated tin in a 150 ml. round-bottomed flask fitted with a small reflux
water-condenser. (A large flask is employed because the mixture when subse-
quently boiled may "bump" violently.) Pour 10 ml. of cone. HCl down the
condenser: on this scale the reaction is not sufficiently vigorous to get out of
control. Heat over a gauze for 15 minutes. Cool the flask and add a solution of
7.5 g. of NaOH in 10 ml. of water to redissolve the initial precipitate. Add about
PREPARATIONS 165
15 ml. of water and fit the flask with a small knee-tube and water-condenser
(Fig. 59, p. ioo). Heat over a gauze and collect the distillate in a small flask: the
aniline distils rapidly in the steam, and the distillate suddenly becomes clear when
about 18 ml. have been collected. Add 3 g. of powdered salt to the distillate,
shake to dissolve and extract twice with about 4 ml. of ether each time. Dry the
ethereal extracts in a 20 ml. conical flask with a few small pieces of solid KOH:
the solution will be dry in about 15 minutes. Carefully decant the ethereal solu-
tion into the flask shown in Fig. 36 (p. 63), taking care that no adhering moisture
or solid falls into the flask; add a small piece of unglazed porcelain or a few
granules of carborundum (which does not absorb the liquid) and place the flask
in a beaker containing hot water. Distil off all the ether with water running
through the condenser, and away from all flames. Then run the water out of the
condenser and heat the flask with a small flame. Attempt to keep the vapour of
the hot aniline around the bulb of the thermometer for about one minute before
actually distilling over the aniline. This is done in order to allow the bulb to
reach the true temperature of the vapour. Collect the fraction of b.p. 180-185°.
Using the pear-shaped flask shown in Fig. 36, it is usually possible to distil
almost to the last drop. Yield, 1-5 g.
For reactions of aniline, see pp. 372-373.

2,4,6-Tribromoaniline. C 6 H 2 (NH 2 )Br 3 .


Aniline undergoes very ready nuclear substitution by bromine even in the
cold, the bromine atoms entering the two ortho positions and the para position
with the formation of symmetric or 2,4,6-tribromoaniline. The presence
C 6 H 6 NH 2 + 3Br, = C e H 2 (NH,)Br, + 3HBr
of the bromine atoms in tribromoaniline reduces considerably the basic
properties of the amino group, and salts even with strong acids are almost
completely hydrolysed in the presence of water, although they can be prepared
in the presence of solvents such as benzene (p. 203).
It should be noted that phenol also reacts very readily with bromine to give
the corresponding 2,4,6-tribromophenol, C 6 H 2 (OH)Br 3 .

Required: Aniline, 4 ml.; bromine, 6-4 ml.


Assemble the apparatus shown in Fig. 65. A 500 ml. Buchner
flask A is fitted with a cork through which passes a glass delivery-
tube B reaching nearly to the bottom of A. B is then connected
by a short piece of rubber tubing to the side-arm of a 150 ml.
distilling-flask C, care being taken to ensure that the two glass
tubes touch one another inside the rubber connection. A narrow
glass tube D is then fitted as shown so that it reaches within 2-3
cm. of the bottom of C.
Dissolve 4 ml. of aniline in io ml. of dilute hydrochloric acid
166 PRACTICAL ORGANIC CHEMISTRY
in A, and then dilute the solution with 200 ml. of water. Now
place 6-4 ml. (20-5 g.) of bromine
(care!) in C, and cover it with
about 40 ml. of cold water. Adjust
the position of the tube D until it
nearly touches the surface of the
bromine layer. Connect A to a
To put
suction water-pump, so that a
steady stream of bromine vapour
is carried over from C into A, where
the greyish-white tribromoaniline
soon begins to separate. Shake the
contents of A from time to time to
FIG. 65. ensure an even distribution of the
tribromoaniline. When the evap-
oration of the bromine has caused the water in C to become
almost colourless (about 40 minutes), stop the current of air,
and filter off the tribromoaniline at the pump, wash well with
water and drain. Recrystallise from rectified spirit, using
animal charcoal: the tribromoaniline is obtained as colourless
crystals, m.p. 120°. Yield, 8*5 g.
For the elimination of the amino group from tribromoaniline, see
p. 202.
/7-Bromoacetanilide, BrC6H4NHCOCH3. (Semi-micro
scale.)
Acetanilide also undergoes ready bromination, with the formation of a
mixture of o- and />-bromoacetanilide. The ortho compound is formed in only
C 6 H 5 NHCOCH 3 + Br2 = BrC 6 H 4 NHCOCH 3 + HBr
small amount, however, and being more soluble in ethanol than the para
compound, can be readily eliminated by recrystallisation.
Required: Acetanilide, i g.; bromine, 0-42 ml.
Dissolve i g. of finely powdered acetanilide in 5 ml. of cold
glacial acetic acid contained in a 25 ml. conical flask. Then in
another small flask prepare a solution* of 0-42 ml. (1-34 g.) of
bromine (care!) in 6 ml. of glacial acetic acid, and add this
solution slowly to the acetanilide solution, shaking the latter
throughout the addition to ensure thorough mixing. Allow the
final mixture to stand at room temperature for 15 minutes. Then
* For class work it is convenient to make up a single bromine solution by
dissolving 7 ml. of bromine in ioo ml. of glacial acetic acid, and using 6-5 ml.
of this solution for each preparation.
PREPARATIONS 167
pour the pale reddish-orange solution, which may already contain
some crystals of p-bromoacetanilide, into a large excess (about
60 ml.) of cold water, whereupon the p-bromoacetanilide will
rapidly crystallise out. Stir these crystals thoroughly with the
water to eliminate acetic acid, unchanged bromine, etc., and then
filter at the pump, wash well with cold water, drain, and finally re-
crystallise from rectified spirit. The p-bromoacetanilidc is
obtained as colourless crystals, m.p. 167°. Yield, i-o g.

/?-Nitroacetanilide, NO 5 C 6 H 4 NHCOCH 35 and p-Nitro-


aniline, NO 2 C 6 H 4 NH 2 .
Aniline cannot be directly nitrated with the usual nitrating mixture of
nitric and sulphuric acid, because considerable charring and oxidation of the
aniline occurs. The difficulty may be overcome either by using a very large
excess of sulphuric acid, or (better) by protecting the reactive amino group by
acetylation, since the acetylamido group, CH 3 CONH -, has the same ortho and
para directing influence as the NH 8 - group itself. Acetanilide undergoes
ready nitration, giving chiefly the colourless p-nitroacetanilide, mixed, how-
ever, \vith a much smaller proportion of the yellow o-nitroacetanilide. Re-
crystallisation from ethanol readily removes the more soluble ortho compound,
and the pure />-nitroacetanilide which separates can then be hydrolysed to
/>-nitroaniline.

Required: Acetanilide, 10 g.; acetic acid, 10 ml,; sulphuric


acid, 20 ml.; fuming nitric acid, 4 ml.
Add 10 g. of powdered acetanilide to 10 ml. (io*6g.) of
glacial acetic acid contained in a ioo ml. beaker, and then to
the well-stirred mixture add 20 ml. (37 g.) of concentrated
sulphuric acid. The mixture becomes hot and a clear solution
is rapidly obtained. Place the beaker in an intimate mixture of
salt and crushed ice until the temperature of the reaction-mixture
falls to about 0-5°. Now, whilst stirring the viscous mixture con-
tinuously with the thermometer, add 4 ml. of ordinary fuming
nitric acid (d, 1*5) cautiously drop by drop from a burette (prefer-
ably in a fume-cupboard), so that the temperature of the mixture
does not rise above 25°: this operation should take 10-15 minutes.
Then remove the beaker from the freezing mixture, allow it to
stand for 30 minutes at room temperature, and pour the con-
tents on to about ioo g. of crushed ice, whereby the crude
nitro-acetanilide is at once precipitated: finally rinse out the
beaker with 50 ml. of water containing a few fragments of ice,
adding the solution to the main bulk of the product. Allow the
mixture to stand for about 20 minutes, and then filter at the
pump, wash thoroughly with cold water to remove acid, and drain.
i68 PRACTICAL ORGANIC CHEMISTRY
Yield of crude product, 14 g., the high value being due to
traces of polynitro-derivatives.
Recrystallise the crude pale yellow product from methylated
spirit, filter at the pump, wash quickly with a few ml. of fresh
spirit, and then drain and dry. The yeJlow o-nitroacetanilide
remains in the filtrate, whilst the p-nitroacetanilide is obtained
as colourless crystals, m.p. 214°. A second recrystallisation of
the para compound should not be necessary. Yield of pure
product, 8 g.

Hydrolysis to p-Nitroaniline. For this purpose use 70%


sulphuric acid, the usual reagent employed for the hydrolysis
of anilides (p. 108). Add 5 g. of the recrystallised p-nitro-
acetanilide to 30 ml. of 70% sulphuric acid, and boil the mixture
gently under a reflux water-condenser for 20 minutes. Then
pour the clear hot solution into about 150 ml. of cold water, and
finally add an excess of sodium hydroxide solution until precipi-
tation of the yellow p-nitroaniline is complete. Cool the mixture
in ice-water if necessary, and then filter at the pump, wash well
with water, and drain thoroughly. The p-nitroaniline is thus
obtained as a dark yellow powder, which has m.p. 147-148° and
therefore, in spite of the dark colour, is practically pure. Yield,
3'S S- (almost theoretical). Recrystallise from a mixture of
equal volumes of rectified spirit and water, boiling the solu-
tion gently with a small quantity of animal charcoal for 3-4
minutes, and then filtering the hot solution through a Buchner
funnel preheated by the filtration of some boiling solvent. The
p-nitroaniline separates in bright yellow crystals, m.p. 148°.
For reactions of />-nitroaniline, see p. 387.

w-Nitroaniline. C 6 H 4 (NO 2 )NH 2 .


w-Nitroaniline, unlike o- and />-nitroaniline, clearly cannot be prepared by
the direct nitration of aniline or of acetanilide. It has therefore to be prepared
by reducing only one of the nitro groups in the readily accessible m-dinitroben-
zene. The earlier method for this purpose consists in boiling an ethanolic
solution of the dinitrobenzene with ammonium sulphide. The latter undergoes
dissociation giving hydrogen sulphide, which reduces the dinitrobenzene to
C,H 4 (N0 2 ) 2 + 3 H 2 S = C 6 H 4 (NO 8 )NH 8 + 2 H 2 O + 3S
w-nitroaniline with liberation of sulphur. The method however is long and
tedious, primarily because the hot ethanolic solution has to be repeatedly cooled
and resaturated with hydrogen sulphide to ensure efficient reduction. Very
much better results are obtained by boiling an aqueous suspension of m-dinitro-
benzene with sodium disulphide solution, prepared by the direct addition of
PREPARATIONS 169
sulphur to sodium sulphide. In these circumstances the dinitrobenzene is
Na2S + S = Na1S,
C8H4(NO1), + Na 2 S 2 + H 2 O = C 6 H 4 (NO 2 )NH, + Na8S8O,
readily reduced to w-nitroaniline, the sodium disulphide being^ oxidised mainly
to sodium thiosulphate.

Required: Sulphur, 4-2 g.; sodium sulphide, 16 g.; m-dinitro-


benzene, 10 g.
The crystalline sodium sulphide (Na 2 S^H 2 O) used to prepare
the disulphide is very deliquescent, and only a sample which has
been kept in a well-stoppered bottle and therefore reasonably dry
should be used. A sample from a badly-stoppered bottle may
contain, in addition to the crystals, a certain amount of aqueous
solution, in which hydrolysis and partial decomposition will have
occurred: such a sample should therefore be rejected. Add
4-2 g. of finely powdered sulphur to a solution of 16 g. of
the crystalline sodium sulphide in 60 ml. of water, and boil the
mixture gently for a few minutes until a clear solution of the
disulphide is obtained.
Heat a mixture of io g. of pure m-dinitrobenzene and 450
ml. of water in a 750 ml. beaker on a sand-bath until the water
boils gently. Transfer the sodium disulphide solution to a small
dropping-funnel, and clamp the funnel in position so that the end
of the stem is immediately above the beaker. Now allow the
disulphide solution to fall drop by drop into the boiling water at
such a rate that the total addition takes 10-15 minutes: through-
out this period keep the molten m-dinitrobenzene vigorously
stirred by means of a glass rod (having the lower end covered by a
short length of rubber tubing) so that the dinitrobenzene is kept
continuously dispersed as fine drops and not allowed to settle to
the bottom. (On a larger scale a mechanical stirrer can be advan-
tageously used at this stage, but with the above quantities hand-
stirring gives excellent results.) When the addition of the
disulphide is complete, boil the solution gently for a further
20 minutes. Then add sufficient hot water to restore the total
volume to at least 500 ml., boil vigorously for a few moments and
quickly filter the solution, using a Buchner funnel and flask which
have been preheated by the filtration of much boiling water: a
small quantity of elementary sulphur remains on the filter. The
pale brown filtrate rapidly deposits yellow crystals of the m-nitro-
aniline. Chill in ice-water, and then filter at the pump, wash
with cold water, and drain. (Yield, 6-5-7-0 g.) Recrystallise
from much hot water (about 80 ml. per g. of nitroanilinc, to
I7Q PRACTICAL ORGANIC CHEMISTRY
allow filtration through a preheated funnel without premature
crystallisation). m-Nitroaniline is thus obtained as bright yellow
crystals, m.p. 114°.
If an impure and discoloured sample of m-dinitrobenzene is
used in the above preparation, add some animal charcoal to the
solution immediately prior to the 20 minutes' boiling: the use of
charcoal is to be avoided when possible, however, as it is liable to
absorb an appreciable quantity of the w-nitroanilinc.
For reactions of w-nitroaniline, see p. 387.

The Nitration of Phenol.


One of the characteristic properties of phenol is the ease with which it gives
substitution products, this property being particularly well shown by the ready
nitration, sulphonation and bromination which the benzene ring in the phenol
molecule undergoes.
If phenol is treated even with dilute nitric acid at room temperature,
nitration readily occurs with the simultaneous formation of the yellow o-nitro-
phenol and the white />-nitrophenol. These compounds can be readily
separated, because the former is volatile, and the latter non-volatile, in steam.
+
(This nitration probably does not involve the NO 3 ion, which is present in a
mixture of concentrated nitric and sulphuric acids.)
If phenol is heated with more concentrated nitric acid (in the presence of
sulphuric acid), nitration occurs ultimately at the para and at both the ortho
positions, giving picric acid or 2,4,6-trinitrophenol. To prepare picric acid,
however, it is more convenient first to heat the phenol with sulphuric acid,
whereby a mixture of o- and ^-phenol sulphonic acids is readily obtained. If
this mixture is now heated with concentrated nitric acid, nitration occurs at the
HOC 6 H 4 H i HOSO 3 H -- HOC 6 H 4 SO 3 H i H 2 O

two positions meta to the - SO3H group in each compound, and finally the
- SO3H group in each of the dinitrophenol sulphonic acids is replaced by a
HOC 8 H 4 SO 3 H + 2HONO 2 = HOC.H2(NO2)2SO3H + 2H,O
HOC 6 H 2 (NOa) 2 SO 3 H -f HONO1 = HOC,H 2 (NO 2 ) 3 + H 8 SO 4
third nitro group, giving picric acid in both cases.

o- and />-Nitrophenols. NO2C6H4OH.


Required: Nitric acid, 25 ml.; phenol, 20 g.
Prepare a mixture of 25 ml. of concentrated nitric acid and 80
ml. of water in a 750 ml. flat-bottomed flask for which a steam-
distillation fitting is available for subsequent use. Warm a
mixture of 20 g. of phenol and 15 ml. of water gently in a
small conical flask until the phenol is molten: on shaking the
PREPARATIONS 171
mixture vigorously an emulsion of the phenol in the water is thus
obtained. Now place a thermometer in the dilute nitric acid,
cool the latter in ice-water, and add the phenol emulsion in small
quantities at a time so that the temperature of the well-shaken
mixture does not rise above 30°. When the addition of the
phenol is complete, remove the flask from the ice-water and allow
the mixture to stand for at least 2 hours—and preferably over-
night. During the first hour of this period of standing, retain
the thermometer in the liquid and occasionally shake the latter
vigorously to ensure thorough mixing: the temperature will
spontaneously rise slowly to 50-55° but should not be allowed to
rise above this upper limit. If the mixture is allowed to stand
for only 2 hours, chill it thoroughly in ice-water at the end of
this period in order to coagulate and partly harden the black
syrupy insoluble residue and so obtain a sharp separation between
this heavy residue and the aqueous layer above. (If the mixture
is allowed to stand overnight, a complete separation will occur
spontaneously.)
Then add ioo ml. of water, shake well to extract excess of acid,
and allow the black oily drops to settle. Then decant the clear
reddish-brown aqueous solution from the heavy black residual
oil: this can readily be done if the nitration mixture has been set
aside overnight, as the oily drops then rapidly sink and collect at
the bottom of the aqueous layer, but if the mixture has been
allowed to stand for only 2 hours, care must be taken that any oily
drops still floating on the surface of the solution are not poured
away with the aqueous solution. Now add 200 ml. of water, repeat
the shaking, when the heavy oil will become semi-solid and the
aqueous layer can readily be poured off. Add 300 ml. of water to
the residue in the flask, fit the latter with the steam-distillation
inlet and outlet tubes, and assemble the complete apparatus for
steam-distillation (Fig. 15, p. 33), using a single-surface glass-
jacketed condenser of wide bore. Steam-distil the mixture until
about 250 ml. of distillate have been collected, the receiver being
meanwhile cooled in ice-water. The o-nitrophenol readily passes
over in the steam and crystallises in the cold distillate. If the
nitrophenol crystallises in the condenser, run out the con-
denser-water for a few moments: the nitrophenol will then soon
melt and pass on into the distillate. When the distillation is
complete (i.e., when a few ml. of the distillate collected in a
test-tube give no crystalline deposit on thorough cooling), cool
the distillate in ice-water for a further few minutes to ensure
complete solidification of the o-nitrophenol, and then filter the
172 PRACTICAL ORGANIC CHEMISTRY
latter at the pump, and drain thoroughly. Yield, 7 g. The
o-nitrophenol so obtained is practically pure. It may be further
purified if desired either by steam-distilling a second time, or by
recrystallisation.
For the latter purpose, dissolve the crystals in hot ethanol, and then add
water drop by drop to the well-stirred solution until a fine emulsion just appears:
then add more ethanol, also drop by drop, until the emulsion just redissolvcs.
Xow allow the solution to cool spontaneously: if the emulsion reappears,
add a few drops of ethanol from time to time in order to keep the solution
clear. Finally the o-nitrophenol separates in crystals, and the \vell-stirred
mixture may now be cooled in ice-water until crystallisation is complete.
Filter, drain and dry either in an atmospheric desiccator, or by pressing between
drying-paper.

The 0-nitrophenol is obtained as bright yellow crystals, m.p.


46°, possessing an odour which resembles both that of phenol and
of nitrobenzene.
Meanwhile to obtain the />-nitrophenol, chill the crude residue
in the steam-distillation flask thoroughly in ice-water for about
20 minutes.* The black tar becomes almost solid, and crystals
of crude p-nitrophenol separate. Filter off the complete solid
product at the pump, wash it with water, and transfer it to a
beaker. Extract the p-nitrophenol by boiling this residue with
about 150 ml. of water, finally decanting off the aqueous solution
and filtering it through a fluted filter-paper directly into a 800 ml.
beaker. Repeat the extraction with a further 150 ml. of boiling
water, and finally a third time with a boiling mixture of 150 ml.
of water and 50 ml. of concentrated hydrochloric acid. Finally
add about 3 g. of animal charcoal to the united filtrate, and then
boil the latter in the open beaker until the volume is reduced to
about ioo ml. Then filter through a small Buchner funnel
which has been preheated by the filtration of some boiling dis-
tilled water. The filtrate on cooling, and finally chilling in ice-
water, deposits the p-nitrophenol as pale brownish-white crystals:
filter at the pump, wash with a small quantity of water and drain.
Yield, 4 g. The p-nitrophenol can be recrystallised with very
little loss from a mixture of equal volumes of water and concen-
trated hydrochloric acid, and is thus obtained as colourless
odourless crystals, m.p. 114°. (If the p-nitrophenol is re-

* The preparation can be shortened by omitting this stage and extracting the
black residue by boiling it first with the water already present in the flask.
In this case the yield of p-nitrophenol is increased somewhat, but the product
is usually very dark in colour.
PREPARATIONS 173
crystallised from hot water alone, it almost invariably separates
first as a fine emulsion, which subsequently crystallises.)
For properties and reactions of o- and />-nitrophenols, see p. 386.

OH
NO 12 /\ NO2
Picric Acid (2,4,6-Trinitrophenol). I^J,
NO2
Required: Phenol, 8 g.; sulphuric acid, 10 ml.; nitric acid
30 ml.
Weigh out 8 g. of phenol into a dry 750 ml. flat-bottomed
flask, add 10 ml. (18-5 g.) of concentrated sulphuric acid, and
shake the mixture, which becomes warm. Now heat the flask
on a briskly boiling water-bath for 30 minutes to complete the
formation of the phenol-sulphonic acid, and then chill the flask
thoroughly in an ice-water mixture. Place the flask on a wooden
block (or on some similar non-conducting surface) in an efficient
fume-cupboard, and without delay, i.e., whilst the phenol-
sulphonic acid is still a cold viscous syrup, add 30 ml. of concen-
trated nitric acid and at once thoroughly mix the liquids by shaking
for a few seconds. Then allow the mixture to stand undisturbed.
Usually within one minute a vigorous (but harmless) reaction
occurs, and red fumes pour out of the flask. When the action
subsides, heat the flask on a boiling water-bath for i J hours, with
occasional shaking. During this period the heavy oil, which is
present at the beginning, ultimately forms a mass of crystals.
When the heating is complete, add ioo ml. of cold water, mix
well and then chill thoroughly in ice-water. Filter the yellow
crystals at the pump, wash thoroughly with water to eliminate all
inorganic acid and drain. Recrystallise from a mixture of i
volume of ethanol and 2 volumes of water, about 90 ml. of the
mixed solvent being required. Picric acid is obtained in pale
yellow leaflets, m.p. 122°, Dry by pressing between sheets of
drying-paper, or in a desiccator. Yield of recrystallised material,
1
S g;
Picric acid if stored in bulk should, for safety, first be damped.
Smaller quantities may be safely kept whilst dry, but should be
stored in bottles having cork or rubber stoppers: glass stoppers
should never be used for potentially explosive substances, because
on replacing the stopper some of the material may be ground
between the neck of the flask and the stopper, and so caused to
explode.
i74 PRACTICAL ORGANIC CHEMISTRY
REACTIONS OF PICRIC ACID, (i) The presence of the three nitro
groups in picric acid considerably increases the acidic properties of the
phenolic group and therefore picric acid, unlike most phenols, will
evolve carbon dioxide from sodium carbonate solution. Show this by
boiling picric acid with sodium carbonate solution, using the method
described in Section 5, p. 330. The reaction is not readily shown by a
cold saturated aqueous solution of picric acid, because the latter is so
dilute that the sodium carbonate is largely converted into sodium
bicarbonate without loss of carbon dioxide.
(2) To a cold aqueous solution of picric acid, add about an equal
volume of dilute potassium cyanide solution. An orange coloration
develops and rapidly darkens to a deep red.
USES OF PICRIC ACID. The following further reactions of picric acid are
used for analytical purposes in the laboratory.
(3) Identification of Aromatic Hydrocarbons. Picric acid combines with
many aromatic hydrocarbons, giving addition products of definite m.p. Thus
with naphthalene it gives yellow naphthalene picrate, C 10 H 81 (NOg) 3 CeH 2 OH,
m.p. 152°, and with anthracene it gives red anthracene picrate,
C M H 10 ,(NO 2 ) 3 C e H 2 OH, m.p. 138°. For practical details, see p. 394.
(4) Identification of Amines. Picric acid combines with many amines to
give crystalline picrates, of general formula 6,(NOg)3C6H8OH, where B is a
molecule of a monacidic base. These picrates have usually sharp melting- or
decomposition-points, and serve to characterise the amines concerned. They
may be formed either by (a) direct union of the acid and the base in a suitable
solvent, or (b) by the interaction of sodium picrate and a salt of the amine in
aqueous solution.
(a) Dissolve 3-4 drops of pyridine in about 3 ml. of ethanol and add a cold
ethanolic solution of picric acid. A yellow precipitate of pyridine
picrate, C 6 H 6 N^NOz) 3 C 6 H 8 OH, at once separates. It may be filtered
off, and recrystallised from ethanol, m.p. 167°. Quinoline similarly
gives quinoline picrate, C 9 H 7 N,(NO 2 ) 3 C 6 H 2 OH, m.p. 203°.
(b) If an cthanolic solution of picric acid is similarly added to one of aniline,
no precipitation occurs, owing to the high solubility of aniline picrate
in ethanol. If, however, a cold aqueous solution of aniline hydro-
chloride is added to a similar solution of sodium picrate and the
mixture shaken, yellow crystals of aniline picrate, m.p. 165°, soon
separate.
(5) Detection of Potassium in the presence of Sodium. Add a cold saturated
aqueous solution of sodium picrate to a solution of potassium chloride. A rapid
precipitation of the less soluble potassium picrate occurs, even from a i° 0
solution of potassium chloride.
Picric acid is used on a large scale as a high explosive, but for this purpose
requires a detonator. If a ffw small crystals of the pure acid are heated on a
crucible lid, they first melt, and ultimately burn harmlessly with a smoky
flame. Metallic salts of picric acid are much less stable than the free acid,
PREPARATIONS 175
and should always be stored damp.
Bromobenzene. C 6H5Br .
If cold benzene is treated with bromine in the absence of sunlight, very little
reaction occurs; if, however, a "halogen carrier," such as iron, iodine, pyridine,
etc., is also present, a rapid reaction by substitution occurs, forming first
C6H. + Br, = C 8 H 5 Br + HBr
bromobenzene, and then mainly p-dibromobenzene.
The reaction must be carried out in the absence of direct sunlight, since
sunlight causes the bromine to add directly on to benzene, particularly if the
C 6 H, + 3Br2 = C 6 H 6 Br 6
latter is warm, to give benzene hexabromide.
Bromination of the aromatic nucleus is now regarded as replacement of a
hydrogen atom of the intact nucleus as a result of an attack by a polarised
complex with a positive end. Iron acts as a "carrier" by forming FeBr3, which
as a Lewis acid forms a polarised complex with one mol. of Br 2 :

FeBr3 -> Br - v - - Br - -_- FeBr3 ^ ' . + FeBr4

I
Br
+ HBr + FeBr 3

Required: Purified benzene, 34 ml.; pyridine, 0-5 ml.; bromine,


24 ml.
The benzene used in this preparation should be reasonably free
from toluene: therefore use a sample of benzene supplied by
dealers as "crystallisable benzene/* i.e., one which crystallises
readily when cooled in ice-water. It should preferably be dried
over calcium chloride and, immediately before use, filtered
through a fluted filter-paper. The pyridine should also prefer-
ably be dried over solid potassium hydroxide and redistilled.
Place 0-5 ml. of the pyridine in a 200 ml. round- or flat-bottomed
flask and add 34 ml. (30 g.) of benzene. Fit the flask with a
reflux water-condenser, and then place it in a cold water-bath.
If the experiment is conducted in a fume-cupboard, the top of
the condenser can be closed with a calcium chloride tube bent
downwards (as in Fig. 61, p. 105; or in Fig. 23(A), p. 45, where the
outlet-tube A will carry the calcium chloride tube) and the hydro-
gen bromide subsequently allowed to escape: if, however, the
experiment is performed in the open laboratory, fit to the top of
the condenser (or to the outlet-tube A) a glass delivery-tube
which leads through a piece of rubber tubing to an inverted glass
funnel, the rim of which dips just below the surface of some water
176 PRACTICAL ORGANIC CHEMISTRY
in a beaker, so that the hydrogen bromide may be absorbed with-
out risk of "sucking back." Ensure that the apparatus is not
standing in the direct rays of the sun.
Now pour 24 ml. (76 g.) of bromine (care in manipulation!)
down the condenser, and at once replace the calcium chloride
tube or the delivery-tube, as a vigorous reaction occurs when
the bromine dissolves in the benzene. When the initial evolu-
tion of hydrogen bromide slackens, heat the water-bath to
25-30° for one hour, occasionally shaking the contents of the
flask: finally raise the temperature of the bath to 65-70° for a
further 45 minutes. Now transfer the dark-coloured liquid to a
separating-funnel and shake with an excess of 10% aqueous
sodium hydroxide solution: the heavy lower layer of crude
bromobenzene becomes almost colourless at this stage. Run off
the bromobenzene, shake it again with water to ensure absence
of alkali, and then dry with calcium chloride for 20-30 minutes.
Filter through a small fluted filter-paper directly into a 50 ml.
distilling-flask fitted with an air-condenser. Now distil the crude
bromobenzene slowly, rejecting the fraction boiling up to 150°,
and collecting that of b.p. 150-160°. Yield, 28-29 g. (about
19 ml.). A small quantity of crude p-dibromobenzene remains
in the flask.
Carefully refractionate the liquid of b.p. 150-160°, either by
direct distillation from a small distilling-flask or (preferably) by
using a short fractionating column, of the type shown in Fig.
U(B), p. 26. Almost pure bromobenzene is thus obtained, of
b.p. 155-156° if a column is used. Yield in either case, about
22 g. (14-15 ml.).
Bromobenzene is a colourless liquid of b.p. 156°, and d, 1*50:
it has a faint agreeable odour. The bromine atom, being directly
joined to the benzene ring, is very inert, and the only common
reactions in which it is split off from the ring are the Fittig
reaction (p. 288) and the Grignard reagent (pp. 280-284).
For reactions of bromobenzene, see p. 390.

The />-dibromobenzene formed as a by-product in the above reaction


usually solidifies when the undistilled residue obtained in the first dis-
tillation is chilled. It may then be isolated by adding about io ml. of
methylated spirit and some animal charcoal to the flask, boiling for a few
minutes, and filtering hot. On cooling the filtrate in ice-water, crystals
of p-dibromobenzene, m.p. 89°, separate: recrystallise a second time if
necessary to obtain colourless crystals.
PREPARATIONS 177
Ethyl y-Bromocrotonate. BrCH2CHiCH-COOC2H5.
(Using N-Bromosuccinimide.)
A T -Bromosuccinimide (prepared by the action of bromine on succinimide
at o° in the presence of sodium hydroxide) is a valuable specific reagent for
brominating defines in the a-methylene position to the double bond without
simultaneously adding bromine to this bond. For example, if A T -bromosuccini-
mide is represented by (C 4 H 4 O 1 )NBr:—

(C 4 H 4 O 2 )NBr-fCH s -CH:CH-COOEt->(C 4 H 4 O8)NH+BrCH 2 -CH:CH-COOEt

The reaction was formerly considered to involve a radical mechanism initiated


by the non-ionic fission of the very weak N-Br bond.
H 2 C-CO H 2 C-CO
I NNBF -* j ^>N + Br
H 2 C-CO H 2 C-CO
H 8 C-CO H 2 C-CO
j \ N --!-CH 3 -CHiCH-COOEt -> j ^)NH + CH 2 CHiCH-COOEt
H 2 C-CO H 2 C-CO
H1C-CO H 2 C-CO -
CH 2 CH:CH-COOEt + ^)NBr -> BrCH 2 -CHrCH-COOEt + ^)N
H2CCO H 2 C-CO

Such a mechanism is supported by the fact that the reaction is accelerated


by benzoyl peroxide and other radical-producing agents. It is now however
considered that the function of the A T -bromosuccinimide is to provide a constant,
very low concentration of molecular bromine (Tedder et al.).
The substitution is best carried out by boiling zV-bromosuccinimide with the
olefine in carbon tetrachloride. Succinimide crystallises out from the carbon
tetrachloride on cooling whereas the brominated product remains dissolved in
the carbon tetrachloride.
Required: Ethyl crotonate, 22-8 g.; A-bromosuccinimide,
35-6 g.; carbon tetrachloride, 40 ml.
Dissolve 22-8 g. of ethyl crotonate in 40 ml. of dry carbon
tetrachloride and add 35 -6 g. of A r -bromosuccinimide.* Heat the
mixture under reflux for three hours. Cool to o° and filter off
the succinimide which is insoluble in cold carbon tetrachloride.
Now shake the filtrate with water in a separating funnel, separate
and dry the carbon tetrachloride layer with sodium sulphate.
Filter through a fluted filter-paper into a Claisen flask and distil
*Add o-2 g. of benzoyl peroxide to accelerate reaction.
178 PRACTICAL ORGANIC CHEMISTRY
off the carbon tetrachloride (b.p. 77°) at atmospheric pressure.
Distil the residue at water-pump pressure. The fraction coming
over below about 58°/i4 m.m. is unchanged ethyl crotonate.
Collect the fraction boiling at 98-99°/14 m.m. This is pure
ethyl y-bromocrotonate, a colourless, mobile liquid having a
strong pleasant odour. Yield, 25 g.
Sulphonation.
A further difference between aliphatic and aromatic hydrocarbons is that
only the latter are capable of direct suiphonation. Thus benzene when heated
with concentrated sulphuric acid gives benzenesulphonic acid, a reaction which
proceeds more readily, however, if chlorosulphonic acid is used instead of sul-
phuric acid: an excess of chlorosulphonic acid however may convert the sul-
phonic acid into the sulphonyl chloride (cf. p. 181).
C 6 H 5 H + HOSO 3 H -> C 6 H 5 SO 3 H + H 2 O
C 6 H 5 H + ClSO3H -> C 6 H 5 SO 3 H + HCl
Aromatic sulphonic acids are frequently difficult to obtain pure, since they
almost invariably decompose on attempted distillation, and many are very
soluble in water: such aqueous solutions on being concentrated often give
syrupy solutions from which the sulphonic acid crystallises with difficulty.
Toluene however sulphonates readily, and the following preparation illus-
trates the rapid formation of toluene-£-sulphonic acid mixed with a small
proportion of the deliquescent o-sulphonic acid, and the isolation of the pure
crystalline />flra-isomer.
The mechanism of aromatic suiphonation is complex and may vary, e.g. with
the concentration of water or oleum in the acid, the temperature, and the hydro-
carbon. One active agent is SO3, and one simplified route may be:

H
SO

This direct suiphonation should be compared with the indirect methods


for the preparation of aliphatic sulphonic acids, e.g., oxidation of a thiol
(RSH -»• RSO SH), and interaction of an alkyl halide with sodium sulphite to
give the sodium sulphonate (RBr + Na1SO, -> RSO8Na + NaBr).

Toluene-p-sulphonic Acid. CH 3 -C 6 H 4 -SO 3 H.


Required: Pure toluene, 30 ml. (26 g.); concentrated sulphuric
acid, 6 ml. (n g.).
Place 30 ml. of pure toluene and 6ml. of concentrated sul-
phuric acid in a i oo ml. conical flask fitted with a reflux water-
condenser. Boil the mixture gently over a gauze for 5 minutes,
with frequent and thorough shaking to mix the two layers. Now
PREPARATIONS 179
cool the mixture (whilst still in the flask) in ice-water, when the
lower layer of the crude sulphonic acid will solidify. Decant off
and discard the upper layer of toluene. Now add 25 ml. of
concentrated hydrochloric acid, attach the condenser, and heat
the mixture gently until a clear solution is just obtained, and
then cool as before. (If the boiling is prolonged, and the con-
centration of the hydrochloric acid thus reduced, the sulphonic
acid will subsequently remain dissolved.) The toluene-p-sul-
phonic acid separates as white crystals, which are contaminated
with the deliquescent o-sulphonic acid. Therefore filter off the
crystals using a small Buchner funnel, drain quickly, and return
the crystals to the flask. Now add 15 ml. of concentrated hydro-
chloric acid and repeat the recrystallisation as before. The
crystalline toluene-p-sulphonic acid can now be drained more
thoroughly at the pump, and should then be dried in a vacuum
desiccator. Yield, 6-3 g. M.p. 103-105°.
A further crystallisation from 15 ml. of hydrochloric acid
gives the sulphonic acid, 5-5 g., m.p. 105°, almost devoid of
deliquescent properties.
On a larger scale, the acid may be purified by dissolving it in
a minimum of cold water, and then saturating the solution with
hydrogen chloride, when the acid will crystallise.
For the preparation of the benzylthiouronium salt, m.p. 182°
see p. 353.

Sulphanilic Acid (/7-Aminobenzenesulphonic Acid).


NH2C6H4SO3H9ZH2O
A second preparation to illustrate sulphonation is that of sulphanilic acid,
NH2C6H4SO3H, a highly crystalline substance which, having a low solubility
in cold water, can be readily isolated. If aniline is treated with an excess of
concentrated sulphuric acid, aniline hydrogen sulphate is first formed, and
then on heating is converted into sulphanilic acid. This conversion into the
sulphanilic acid is, however, very slow with concentrated sulphuric acid: if
C 6 H 5 NH 8 + H1SO4 = C e H 5 NH,,H t SO 4
C 6 H 6 KH 81 H 8 SO 4 = NH 2 C 6 H 4 SO 3 H + H8O
fuming sulphuric acid is used, the sulphonation proceeds much more rapidly,
but the aniline undergoes a certain amount of charring and decomposition on
the addition of the stronger acid. It is best, therefore, first to add concentrated
sulphuric acid to the aniline, and then to add fuming sulphuric acid to the more
resistant aniline hydrogen sulphate so formed: under these conditions little
decomposition occurs, and sulphonation proceeds readily on heating.
Required: Aniline, 10 ml.; sulphuric acid, 20 ml.; fuming
i8o PRACTICAL ORGANIC CHEMISTRY
sulphuric acid (10%), 20 ml.
Place io ml. (10-3 g.) of aniline in a 150 ml. conical flask,
and add slowly 20 ml. (37 g.) of concentrated sulphuric acid;
shake the mixture gently during the addition, and keep it cool by
immersing the flask occasionally in cold water. White lumps of
aniline hydrogen sulphate separate. Add cautiously 20 ml. of
io % fuming sulphuric acid (i.e., concentrated sulphuric acid
containing 10% of dissolved sulphur trioxide), and then heat the
mixture in an oil-bath at 180-190° for i hour, preferably in a
fume-cupboard. Allow the product to cool, and pour it carefully
into about 200 ml. of cold water, stirring the mixture vigorously
during the addition. Allow to stand for about 5 minutes, and
then filter off at the pump the sulphanilic acid which has crystal-
lised out, wash it well with water, and drain. The crystals so
obtained should be almost colourless. Purify by recrystallising
from about 250 ml. of boiling water: filter the hot solution
through a Buchner funnel and flask which have been preheated
by the filtration of boiling distilled water. If, however, the
temperature of the reaction mixture has been allowed to rise
above 190°, the crude sulphanilic acid may be greyish-brown in
colour: in this case, boil the aqueous solution obtained during
the recrystallisation with about 2 g. of animal charcoal for
10-15 minutes (see p. 23), and then filter the hot solution
through the preheated Buchner funnel. The sulphanilic acid
rapidly separates from the filtrate in colourless crystals: when
the filtrate is quite cold, filter off the crystals at the pump, wash
with a small quantity of cold water and drain thoroughly. Dry
the crystals by pressing between sheets of drying-paper, or by
placing in an atmospheric calcium chloride desiccator. In a
vacuum desiccator the sulphanilic acid loses its water of crystal-
lisation, and hence its crystalline form. Yield, about io g.
Sulphanilic acid has no melting-point, as it decomposes on being
heated. It is only slightly soluble in cold water, but easily soluble in
boiling water. The strongly acid sulphonic group suppresses consider-
ably the basic properties of the amino-group: consequently although the
substance will act as an acid, forming salts with alkalis, it will not usually
act as a base to form salts with acids. It is probable that sulphanilic
acid exists as a doubly charged ion, H3NC6H4SO3.
For reactions of sulphanilic acid, see p. 384.
One of the chief uses of sulphanilic acid is in the preparation of coloured
derivatives of the methyl-orange type (p. 214).
PREPARATIONS 181
Sulphanilamide (/>-Aminobenzenesulphonamide).
NH 2 -C 6 H 4 -SO 2 NH 2 .
Sulphanilamide, the simplest member of a large series of bacteriostatic drugs,
can readily be prepared by the following reactions. Acetanilide, when treated
with an excess of chlorosulphonic acid, gives />-acetamidobenzenesulphonyl
chloride (Reaction A), which readily reacts with ammonia to give />-acetamido-
benzenesulphonamide (Reaction B). The acctamido-group in the latter
CH 3 CO-NHC 6 H 5 -f HOSO 2 Cl = CH3CO NH C^H4-SO1Cl + H,O (A)
CH 8 CO-NH C 4 H 4 -SO 2 Cl -f- 2NH 8 = CH 1 CO-NH-0,H 4 -SO 1 NH 1 -f- NH 4 Cl
(B)
CH 8 CO-NH-C 6 H 4 SO 8 NH 8 -^H 1 O = NH 3 -C 8 H 4 -SO 8 NH, -f CH8COOH (C)
compound can be readily hydrolysed under conditions which leave the sulphon-
amido group unaffected, and Sulphanilamide can thus be obtained (Reaction C).
Note that p-acetamidobenzenesulphonyl chloride \\ill similarly react with
primary and secondary amines, and the products, after hydrolysis of the acetyJ
group, may furnish notable drugs: e.g.> the condensation products with 2-
amino-pyridine and 2-aminothiazole, after removal of the acetyl groups,
provide the drugs commonly known as sulphapyridine (M & B 693) and
sulphathiazole respectively.
Required: Acetanilide, 25 g.; chlorosulphonic acid, 63 ml.;
aqueous ammonia (d, 0-880), 120 ml.
p-ACETAMIDOBENZENESULPHONYL CHLORIDE.
(Reaction A.) Carefully add 25 g. of dry powdered acetanil-
ide, with occasional shaking, to 63 ml. (no g., i.e., 5 molecu-
lar equivalents) of chlorosulphonic acid* contained in a 250 ml.
conical flask (fume-cupboard), and then heat the solution to
60-70° for 2 hours. Cool the mixture and pour it carefully on to
about 500 g. of crushed ice, whereupon the sulphonyl chloride
separates as a white solid. Filter off the sulphonyl chloride at the
pump, wash it thoroughly with water, and drain. This crude
product (weight when dry, ca. 38 g.) is sufficiently pure to use
directly in the next stage. A small sample may be dried and
recrystallised from chloroform, and is finally obtained as colour-
less crystals, m.p. 149-150°.
p-ACETAMIDOBENZENESULPHONAMIDE. (Reac-
tion B.) Place the above crude damp sulphonyl chloride in a

* The chlorosulphonic acid should be handled with great care, and always in a
fume r cupboard. The technical acid is usually pure enough for the above
preparation. If it is dark in colour, it can be further purified by careful distilla-
tion (preferably in an all-glass apparatus) and the fraction of b.p. 149-152°
collected for use.
182 PRACTICAL ORGANIC CHEMISTRY
500 ml. conical flask and cautiously add 120 ml. of concentrated
ammonia solution (d, o-88o) (fume-cupboard): a vigorous reac-
tion with evolution of heat will follow. Stir the mixture until a
smooth thin paste is obtained, and then heat at 70° for 30 minutes
with occasional stirring. Cool the mixture and make it just acid
with dilute sulphuric acid. Filter off the precipitated p-
acetamidobenzenesulphonamide at the pump, wash it well
with cold water, and drain it thoroughly. (Yield almost theoreti-
cal.) Again, this material is pure enough for the next stage: a
sample may be recrystallised from hot water and the pure
sulphonamide obtained as colourless crystals, m.p. 219°.
SULPHANILAMIDE. (Reaction C.) Add 15 g. of the
above thoroughly drained sulphonamide to 10 ml. of concen-
trated hydrochloric acid diluted with 20 ml. water, and boil the
mixture gently under reflux for i hour. Then add 30 ml. of
water and heat the mixture again to boiling, with the addition
of a small quantity of animal charcoal. Filter the boiling solution,
and add powdered sodium carbonate in small quantities to the
filtrate with stirring until all effervescence ceases and the
sulphanilamide is precipitated as a white powder. Cool the
mixture thoroughly and filter off the sulphanilamide at the pump,
wash with water and dry. Yield, ca. 10 g.
Purify by recrystallisation from hot water: the sulphanilamide
is obtained as colourless crystals, m.p. 163°.
Diazotisation.
Aromatic primary amines differ markedly from aliphatic amines in their
reaction with nitrous acid. Thus a cold aqueous solution of mono-ethylamine
hydrochloride reacts with nitrous acid to give mainly the corresponding primary
alcohol:
C,H8NHt,HCl + HONO = CtHsOH + H1O + N, + HCl.
Aniline hydrochloride under similar conditions gives, however, benzenediazo-
nium chloride, sometimes called diazo-benzene chloride:
+ -
C4H6NH,,HC1 + HONO = C.H, NCl + *HtO
III
N
Diazonium compounds are usually very soluble in water, and cannot be readily
isolated, since on warming their aqueous solutions, decomposition occurs
with the formation of a phenol:

C 6 H 5 NCl + HOH = C6H6OH + N, + HCl


111
N
PREPARATIONS 183
When an aqueous solution of benzenediazonium chloride is added to a cold
concentrated solution of potassium hydroxide, the unstable potassium diazo-
tate, C 6 H 6 NiNOK, is formed, and this when heated with alkali to 130°
changes to the isomeric but far more stable potassium isodiazotate: it is probable
that these compounds have the structures (A) and (B) respectively.
C6H6N C,HSN
(A) I] —> I (B)
KON NOK
In preparing an aqueous solution of a diazonium salt, such as benzene-
diazonium chloride, it is usual to dissolve the amine in a slight excess
(about 2-2 molecular equivalents) of dilute hydrochloric acid (or alterna-
tively to dissolve the crystalline amine hydrochloride in 1*2 equivalents
of the acid) and then add an aqueous solution of a metallic nitrite.
Nitrous acid is thus generated in situ, and reacts with the amine salt to
give the diazonium compound. For a successful preparation of an
aqueous solution of the diazonium salt, however, two conditions must
always be observed:
(1) The solution of the aniline hydrochloride should be cooled to
5°C., and this temperature maintained throughout the addition of
the sodium nitrite solution. External cooling has to be maintained,
otherwise the heat of the reaction would cause the temperature to rise,
with the consequent decomposition of the diazonium chloride and the
production of phenol. If, on the other hand, the temperature is reduced
to about o°, diazotisation becomes extremely slow and unchanged
nitrous acid may remain in the solution for an impracticably long time.
(2) Sufficient sodium nitrite must be added to diazotise all the aniline
present, otherwise the unchanged aniline will react with the diazonium
chloride to give diazoaminobenzene (p. 187):
C 6 H 5 N 2 Cl + HNHC 6 H 5 -> C 6 H 5 N 2 NHC 6 H 5 + HCl.
To ensure the presence of a slight excess of nitrous acid, potassium
iodide-starch paper is sometimes used as an external indicator, a drop
of the solution being removed from time to time during the addition of
the sodium nitrite, and then dropped on to the paper. When an excess
of nitrous acid is present, iodine is liberated, and gives the familiar
2HNO2 + 2HCl + 2KI = 2NO + 2KCl + I 2 + ^H2O
blue colour with starch. In actual practice, however, it is found that
long before the addition of the theoretical quantity of sodium nitrite is
complete, the solution will give a blue coloration (presumably by
atmospheric oxidation) within a few seconds of being placed on the
Kl-starch paper. If this indicator is used, therefore, it should be
noted that an excess of nitrous acid is not present until an immediate
blue colour is obtained when a drop of the solution is placed on the
paper.
The use of Kl-starch paper is definitely not recommended, however:
184 PRACTICAL ORGANIC CHEMISTRY
it is better to use sodium nitrite* of good quality and to add an amount
which is about 10% in excess of that theoretically required.
The student is recommended to carry out the preparation of iodo-
benzene in order to gain experience in the preparation of aqueous
solutions of diazonium compounds, and then to prepare a solution of
benzenediazonium hydrogen sulphate with which to carry out the chief
reactions that diazonium compounds undergo.

lodobenzene. C 6H6L
When potassium iodide or hydrogen iodide is added to an aqueous solution
of a diazonium salt, nitrogen is readily evolved (no catalyst being necessary)
and the corresponding iodo-compound is formed. lodo-compounds can thus
C 6 H 6 NjCl + KI = C 6 H 6 I + N, + KCl
be readily obtained from aromatic primary amines.

Required: Aniline, 15 ml.; hydrochloric acid, 40 ml.; sodium


nitrite, 12*5 g.; potassium iodide, 35 g.
Dissolve 15 ml. (15*4 g.) of aniline in a mixture of 40 ml.
of concentrated hydrochloric acid and 40 ml. of water contained
in a 250 ml. conical flask. Place a thermometer in the solution,
immerse the flask in a mixture of ice and water, and cool until
the temperature of the stirred solution reaches 5°. Dissolve
12 5 g. of powdered sodium nitrite in 30 ml. of water, and add
this solution in small quantities (about 2-3 ml. at a time) to the
cold aniline hydrochloride solution, meanwhile keeping the
latter well stirred by means of a thermometer. Heat is evolved
by the reaction, and therefore a short interval should be allowed
between consecutive additions of the sodium nitrite, partly to
allow the temperature to fall again to 5°, and partly to ensure that
the nitrous acid formed reacts as completely as possible with
the aniline. The temperature must not be allowed to rise above
10°, otherwise appreciable decomposition of the diazonium com-
pound to phenol will occur: on the other hand, the temperature
should not be allowed to fall as low as o°, as at this temperature
diazotisation becomes very slow, and free nitrous acid may remain
in the solution for a considerable time.
When all the sodium nitrite has been added and diazotisation is
complete, transfer the cold solution to a 600 ml. round-bottomed
bolt-head flask. Dissolve 35 g. of potassium iodide in 50 ml.
of water, and add this solution slowly with shaking to the cold
* Hence all the following preparations involving diazotisation are based on
the use of " Sodium Nitrite Recryst." and not "Sodium Nitrite Technical" or
"Commercial,"
PREPARATIONS 185
diazo solution. A vigorous reaction occurs, nitrogen being freely
evolved, and some iodine being liberated owing to the slight excess
of nitrous acid present. Allow the complete mixture to stand for
10 minutes with occasional shaking, and then heat it on a boiling
water-bath for a further 20 minutes to complete the reaction: the
crude iodobenzene separates as a heavy dark oil at the bottom of
the flask. Add 10% sodium hydroxide solution to the mixture
until the latter is definitely alkaline, i.e., until a drop withdrawn
on a glass rod imparts a definite blue colour to red litmus-paper:
this converts any phenol which may have been formed into
sodium phenoxide which (unlike phenol itself) is not volatile in
steam. Now equip the flask for steam-distillation (Fig. 15, p. 33),
and steam-distil the mixture until no more oily drops of iodo-
benzene come over with the aqueous distillate. Transfer the
distillate to a separating-funnel, and carefully run off the heavy
lower layer of iodobenzene into a small conical flask, rejecting the
upper aqueous layer. (The iodobenzene should now have a pale
yellow colour. If it is dark in colour, return it to the funnel, and
shake it vigorously with a dilute aqueous solution of sodium
thiosulphate until a pale yellow colour is obtained: then run off
the heavy lower layer as before.) Add a few pieces of granular
calcium chloride to the liquid in the conical flask, and shake for
about 10 minutes until the liquid is clear and dry. Filter through
a small fluted filter-paper directly into a 60 ml. distilling-flask.
Fit the flask with a thermometer reading up to at least 200°, and
with a short air-condenser about 12 inches long. Distil the liquid
slowly, and collect the fraction boiling at 185-190°. Yield, about
28 gms. (15-16 ml.).
Iodobenzene, as usually prepared, is a very pale yellow liquid
of b.p. 188°, and d, 1-83. The freshly distilled pure liquid is
colourless, but soon redevelops the yellow colour on exposure to
light. Iodobenzene is insoluble in water.
The iodine atom in iodobenzene (unlike that in the corresponding aliphatic
compounds) is very resistant to the action of alkalis, potassium cyanide, silver
nitrite, etc. This firm attachment of the iodine atom to the benzene ring is
typical of aromatic halides generally, although in suitably substituted nitro-
compounds, such as chloro-2,4-dinitrobenzene, the halogen atom does possess
an increased reactivity (p. 262).

Iodobenzene Dichloride C6H5ICI2, lodosobenzene, C6H5IO,


and lodoxybenzene, C6H1JO,.
When iodobenzene in chloroform solution is treated with chlorine, the iodine
186 PRACTICAL ORGANIC CHEMISTRY
becomes trivalent by the addition of chlorine, and iodobenzene dichloride is
formed. The latter can be regarded as a salt of the basic iodosobenzene,
which can be readily obtained by treating the dichloride with sodium hydroxide.
C6H5ICl1 -f 2NaOH = C 6 H 8 IO + 2NaCl + H 4 O
Iodosobenzene forms similar salts with other acids; dilute nitric acid gives
the dinitrate, C 6 H 5 I(NO 3 ) 2 , and acetic acid the diacetate, C 6 H 5 I(OOCCH 3 ) 2 .
When iodosobenzene is boiled with water, interaction occurs with the
formation of one equivalent of iodobenzene and one of iodoxybenzene:
2C4H1IO = C,H6I + C 6 H 6 IO,
the iodobenzene steam-distils off, whilst the iodoxy-benzene dissolves in the
hot water and rapidly crystallises on cooling.
IODOBENZENE-DICHLORIDE. If a cylinder of chlorine is not available
for this preparation, generate the chlorine by allowing concentrated
hydrochloric acid to fall from a dropping-funnel which is fitted into
the neck of a Buchner flask containing coarsely powdered potassium
permanganate, aiding the reaction when necessary by gentle warming
on a water-bath: purify the chlorine by passing it through wash-bottles
containing water and sulphuric acid respectively. Chlorine from a
cylinder may be used directly without washing.
Dissolve 5 ml. (9-2 g.) of iodobenzene in 35 ml. of chloroform
contained in a wide boiling-tube or in a conical flask. Cool the latter in
ice-water and then pass a steady stream of chlorine through the solution
until no further precipitation of the yellow crystals of iodobenzene
dichloride occurs. Then filter the latter at the pump, and wash with
a small quantity of chloroform. Yield, 11-12 g. The dichloride
slowly decomposes on standing, giving chiefly p-chloroiodobenzene
and hydrogen chloride: C6H6ICl2 '-+ ClC6H4I* -f HCl. Its melting-
point is therefore uncertain, but a freshly prepared dry sample usually
melts at 101-103° with decomposition.
IODOSOBENZENE. The hydrolysis of the dichloride may be carried
out using either sodium hydroxide or pyridine: the former gives the
better product.
(a) Add 4 g. of the finely powdered dichloride to 40 ml. of io%
sodium hydroxide solution contained in a conical flask and shake the
mixture vigorously. A rapid reaction follows, and the yellow colour of
the dichloride fades. Shake at intervals over a period of 20 minutes,
and then filter at the pump, wash with 10% sodium hydroxide solution,
then repeatedly with water, drain thoroughly and dry. Yield, theoretical
(2'9 g-)-
(b) Dissolve 4 g. of the dichloride in 12 ml. of pyridine, and then
dilute the mixture by slowly adding 150 ml. of water, stirring vigorously
throughout the addition. The iodosobenzene separates at first as a
fine emulsion, which rapidly crystallises. Filter, wash with water, and
dry. Yield, 2 g.
Melting-point determinations should not be attempted with iodoso-
PREPARATIONS 187
benzene, as it explodes violently at about 220°.
IODOBENZENE DiACETATE. Add 2 g. of iodosobenzenc to 6 ml. of
glacial acetic acid, boil gently until a clear solution is obtained, and then
cool. The diacetate is freely soluble in acetic acid, but not in ether.
Therefore add ether (about 50 ml.) in order to precipitate the iodoben-
zene diacetate, which rapidly separates in colourless crystals, particu-
larly on scratching with a rod. Filter, wash with ether, and dry. M.p.
157°. Yield, 2 g. The diacetate so obtained is pure, but may if de-
sired be recrystallised from benzene. Unlike the dichloride, it is stable
on being kept.
IODOXYBENZENE. Add 3 g. of iodosobenzene to about ioo ml.
of water contained in a small flask, and steam-distil the mixture until
iodobenzene ceases to come over and the distillate leaving the con-
denser is no longer turbid (usually about 20 minutes). The residual
solution in the flask should now be clear: pour it quickly into a beaker
and cool. (If the residual solution is not clear, it should be filtered
rapidly, using a small Buchner funnel and flask preheated by the filtra-
tion of boiling distilled water, as the iodoxybenzene begins to separate
very rapidly on cooling.) Filter off the colourless crystals of iodoxy-
benzene, wash with water, and dry. Yield, i g.
Alternatively, if it is not desired to collect the iodobenzene, the iodoso-
benzene can be added to about 150 ml. of water contained in an open
beaker or conical flask, and the mixture gently boiled until a clear
solution is obtained and the pale yellow colour has disappeared. On
cooling the iodoxybenzene rapidly separates.
Iodoxybenzene on being heated explodes at 236-237°, and a m.p.
determination should not be attempted.

Benzenediazonium Hydrogen Sulphate, C 0 H 1 N 2 HSO 4 ,


in aqueous solution.
Required: Aniline, 5 ml.; sodium nitrite, 4-5 g.
Dissolve 5 g. (5 ml.) of aniline in 50 ml. of warm dilute sulphuric
acid in a conical flask and add 50 ml. of water. Place a thermometer in
the solution, immerse the flask in a mixture of ice and water, and cool
until the temperature of the stirred solution falls to 5°. Dissolve 4-5 g.
of powdered sodium nitrite in 20 ml. of water, and add this solution in
small quantities (about 2-3 ml. at a time) to the cold aniline sulphate
solution. Keep the latter well shaken and maintain the temperature at
about 5° (see p. 183). When all the sodium nitrite solution has been
added, transfer about 5 ml. of the cold solution to a test-tube for each of
the following reactions. The remainder of the diazonium hydrogen
sulphate solution must be kept in ice-water until required, and then
when all the reactions have been carried out, the solution should be
poured down the sink.
(i) Boil the solution gently for 1-2 minutes. Nitrogen is rapidly
evolved, and phenol is formed in solution. Cool the solution (which
188 PRACTICAL ORGANIC CHEMISTRY
C 6 H 5 X 2 HSO 4 - HOH - C 6 H 5 OH - X 2 - H 2 SO 4
should smell of phenol) and test for phenol by adding bromine water.
A brownish-white precipitate of tribromophenol is produced (p. 339).
(2) To the cold solution, add about 2 ml. of io% potassium iodide
solution. A brisk effervescence of nitrogen occurs, and iodobenzene
separates, usually as drops so small that in spite of their density they
float on the surface.
C 6 H 5 N 2 HSO 4 -r KI -> C 6 H 5 I + N, + KHSO4
(3) (a) Dissolve about 0-5 g. of phenol in a considerable excess of
10% sodium hydroxide solution and cool in ice-water. Pour the diazo-
nium solution into this sodium phenoxide solution and note the forma-
tion of an orange-yellow solution of the sodium derivative of benzene-
azophenol.
C 6 H 5 N 2 HSO 4 + HC 6 H 4 ONa -> C 6 H 5 NtNC 6 H 4 ONa -f- H 2 SO 4
The sulphuric acid is of course neutralised at once by the alkaline
solution.
(b) Repeat, using 0-5 g. of 2-naphthol instead of the phenol. A
scarlet precipitate of benzeneazo-2-naphthol is similarly produced.
C 6 H 5 N 2 HSO 4 + HC10H6OH -> C 6 H 5 NiNC 10 H 6 OH + H 2 SO 4
The above condensations occur only in alkaline solution, hence the
need of an excess of sodium hydroxide in the phenol solutions.
(4) (a) To i ml. of the diazonium solution, add 0-5 ml. of aniline, and
shake vigorously. Diazoaminobenzene separates as a finely-divided
yellow solid.
C6H5N2HSO4 + HNHC 6 H 5 -> C 6 H 5 NiNNHC 6 H 5 + H2SO1
(b) Repeat, using 0-5 ml. of dimethylaniline in place of aniline. A
red solution of benzeneazo-p-dimethylaniline hydrochloride is pro-
duced on adding dil. hydrochloric acid. Add an excess of sodium
C 6 H 5 N 2 HS0 4 +HC 6 H 4 N(CH 3 ) 2 , HC1^C 6 H 5 N 2 C 6 H 4 N(CH 3 ) 2 , HCl
-f H2SO4
hydroxide solution in order to liberate the free base, which is yellow.
(5) Add 2 ml. of ethanol to the solution, shake the mixture and
warm gently. Phenetole (ethyl phenyl ether) is the main product.
C 6 H 5 N 2 HSO 4 + HOC 2 H 5 ->• C 6 H 5 OC 2 H 5 + N 2 + H 2 SO 4
At the same time, the ethanol reduces some of the diazonium compound
to benzene, the ethanol itself being oxidised to acetaldehyde, the odour
C 2 H 5 OH = CH 3 CIIO -J- aH
C 6 H 5 N 2 HSO 4 + zH - C 6 H 6 + N 2 -f H 2 SO 4
of which can sometimes be detected.
PREPARATIONS 189
Chlorobenzene. C6H5Cl. (Sandmeyer's Method.)
Chlorobenzene may be obtained from an aqueous solution of benzenediazo-
nium chloride by two methods:
(a) Gattermann's Method. The addition of finely divided copper powder to
the benzenediazonium chloride solution has a catalytic action even at room
C 9 H 5 N 8 Cl = C6H6Cl + N 2
temperature, causing the evolution of nitrogen and the formation of chloro-
benzene.
(b) Sandmeyer's Method. If the aqueous solution of benzenediazonium
chloride is added to a solution of cuprous chloride in hydrochloric acid and the
mixture then warmed, a similar decomposition occurs, nitrogen and chloro-
benzene being formed.
Required: Copper sulphate, 28 g.; sodium chloride, 9-5 g.;
sodium bisulphite, 14 g.; hydrochloric acid, 70 ml.; aniline,
20 ml.; sodium nitrite, 17 g.
To prepare the solution of cuprous chloride, add 28 g. of
crystalline copper sulphate and 9-5 g. of sodium chloride in
turn to ioo ml. of water in a 250 ml. beaker, and warm the
mixture to 55-60°, stirring it with a thermometer until a clear
solution is obtained at this temperature. Now reduce this solu-
tion either by adding a solution of 14 g. of sodium bisulphite in
25 ml. of water, whereupon the mixed solutions will rapidly be-
come green in colour, or, if a syphon of liquid sulphur dioxide is
available, by passing a brisk current of sulphur dioxide into the
solution. By either method, the cupric chloride formed by the
interaction of the cupric sulphate and the sodium chloride is
reduced to cuprous chloride, which separates as a white powder
as the solution cools. Now place the beaker in cold water con-
taining a small quantity of ice in order to cool the solution to about
10-15°, and thus to complete the separation of the cuprous
chloride: it is important that the solution is not cooled below
this temperature, otherwise crystals of sodium sulphate, etc., may
separate and contaminate the cuprous chloride. Allow the
solution to stand in the cold water whilst the diazotisation of the
aniline is being performed; then filter off the cuprous chloride
rapidly through a Buchner funnel at the pump, wash it once with
a few ml. of distilled water, and then, immediately it is well
drained, transfer it to a mixture of 20 ml. of concentrated hydro-
chloric acid and 20 ml. of water in a 6oo ml. round-bottomed flask.
During the draining of the cuprous chloride on the filter, slight
atmospheric oxidation may give the surface of the chloride a blue
colour: the cuprous chloride will, however, dissolve in the hydro-
chloric acid to give a clear brownish-coloured solution. Attach a
I9Q PRACTICAL ORGANIC CHEMISTRY
reflux water-condenser to the flask, and in the top of the con-
denser fit a dropping-funnel securely by a cork which has a
shallow groove cut or filed vertically down the side, in order to
allow the subsequent escape of nitrogen. (Alternatively, use the
apparatus shown in Fig. 23(A), p. 45.)
Meanwhile, during the cooling of the cuprous chloride solution,
prepare a solution of benzenediazonium chloride by dissolving 20
ml. (20*5 g.) of aniline in a mixture of 50 ml. of concentrated
hydrochloric acid and 50 ml. of water, and after cooling to 5°,
adding slowly a solution of 17 g. of sodium nitrite in 40 ml. of
water. Observe carefully the general conditions for diazotisation
given in the preparation of iodobenzene (p. 184).
When the preparation of the cuprous chloride is complete, place
the diazonium solution in the dropping-funnel at the top of the
reflux condenser, and then heat the flask containing the cuprous
chloride on a boiling water-bath. When the cuprous chloride
solution has been thoroughly heated, remove the water-bath,
support the flask on a stand, and allow the diazonium solution to
run slowly drop by drop down the condenser, meanwhile shaking
the flask gently to ensure thorough mixing. As each drop of the
diazo solution enters the liquid in the flask, a momentary separa-
tion of a yellow addition product, C 6 H 5 N 2 CIjCu 2 Cl 2 , occurs: this
compound then breaks down, giving nitrogen and chlorobenzene,
and the heat of the reaction maintains the temperature of the
solution well above 6o°. When all the diazonium solution has
been added, allow the mixture to stand for 10 minutes, and then
replace the flask on the boiling water-bath for a further 15 minutes
in order to complete the reaction. Then detach the flask, equip it
for steam-distillation (Fig. 15, p. 33) and steam-distil the contents
until no more oily drops of chlorobenzene pass over. Place the
distillate in a separating-funnel, and run off the lower layer of
chlorobenzene into a small conical flask: add a few pieces of
granular calcium chloride, allow to stand for 15-20 minutes, and
then filter the dry chlorobenzene directly into a 60 ml. distilling-
flask. Fit the flask with an air-condenser, and distil the chloro-
benzene, collecting the fraction which boils at 130-135°. Yield
18-19 g.
Chlorobenzene is a stable colourless liquid having b.p. 132°
and d, i - i i ; it is insoluble in water.
For reactions of chlorobenzene, see p. 340.
Benzonitrile (Phenyl Cyanide). C6H5CN. (Sandmeyer's
Method.)
Sandmeyer's method for the preparation of chlorobenzene can similarly be
PREPARATIONS 191
extended to the preparation of bromobenzene and of cyanobenzene or benzo-
nitrile. Thus an aqueous solution of benzenediazonium chloride on treatment
with a solution of cuprous bromide in hydrobromic acid gives nitrogen and
bromobenzene: alternatively, on treatment with a solution of potassium cupro-
cyanide, K 3 [Cu(CN) 4 ], it gives nitrogen and cyanobenzene (or benzonitrile),
C 6 H 5 CN. No similar catalyst is required for the preparation of iodobenzene
(p. 184).
Potassium cupro-cyanide is the most convenient form in which cuprous
cyanide can be used in Sandmeyer's Reaction. It is prepared by adding an
excess of potassium cyanide to copper sulphate solution, whereby the cupric
cyanide which is formed immediately breaks down to give cuprous cyanide and
cyanogen, and the cuprous cyanide then dissolves in the excess of potassium
CuSO4 + zKCN = Cu(CN) 8 -f K 2 SO 4 2Cu(CN) 2 = Cu 2 (CN) 2 + C 2 N 8
6KCN + Cu 2 (CN) 2 = 2K 8 [Cu(CN) 4 ]
cyanide to give potassium cupro-cyanide.

Required: Aniline, 20 ml.; hydrochloric acid, 50 ml.;


sodium nitrite, 17 g.; copper sulphate, 55 g.; potassium cyanide,
60 g.
Apart from the diazotisation, the whole of the following prepara-
tion up to the completion of the steam-distillation must be carried
out in a fume-cupboard having a vigorous draught.
Prepare a solution of benzenediazonium chloride from 20 ml.
(20-5 g.) of aniline precisely as in the preparation of chloro-
benzene (p. 189), i.e., by dissolving the aniline in a mixture of
50 ml. of concentrated hydrochloric acid and 50 ml. of water,
cooling to 5°, and then cautiously adding a solution of 17 g. of
sodium nitrite in 40 ml. of water to the well-cooled and stirred
aniline hydrochloride solution so that the temperature of the
mixture remains between 5° and 10°.
Then, while the diazonium solution is standing in ice-water,
dissolve 55 g. of powdered copper sulphate (CuSO 4 ^H 2 O) in
200 ml. of water contained in a 1500 ml. flat-bottomed flask, for
which a steam-distillation fitting is available for subsequent use.
Place a thermometer in the copper sulphate solution and warm
the latter to 60-65°. Now cautiously add a solution of 60 g. of
powdered potassium cyanide* in ioo ml. of water to the copper
* The "double salt," i.e., potassium cyanide mixed with sodium cyanide, is
best and cheapest for this purpose, and can be obtained already powdered, in
which form, however, storage in an air-tight receptacle is particularly necessary.
If only fused or lump cyanide is available, great care should be taken when
powdering the material in a mortar, in order to prevent small fragments from
flying up and adhering to the lips, nostrils, or eyes. This is best achieved by
draping a duster tent-wise around the pestle and over the mortar, so that the
cyanide is completely covered while it is being crushed.
192 PRACTICAL ORGANIC CHEMISTRY
sulphate solution, shaking the flask during the addition to facili-
tate the evolution and escape of the cyanogen—take £reat care to
avoid inhaling traces of the cyanogen. During the addition of the
cyanide solution the temperature of the mixture rises a few de-
grees (usually to about 75°), and finally a clear pale-brown solu-
tion of potassium cupro-cyanide is obtained.
Now add the diazonium solution to the potassium cupro-
cyanide in small quantities at a time so that the temperature of
the mixture remains between 60° and 70°: shake the mixture vigor-
ously after each addition of the diazo solution. Then fit a reflux
air- or water-condenser to the flask, and heat the latter on a
boiling water-bath for 15 minutes to complete the reaction.
Finally steam-distil the solution until no more oily benzonitrile
passes over (usually until about 600 ml. of distillate have been
collected).
Place the distillate in a separating-funnel and extract the
benzonitrile twice, using about 30 ml. of ether for each extraction.
Return the united ethereal extracts to the funnel and shake with
10 % sodium hydroxide solution to eliminate traces of phenol
formed by decomposition of the benzenediazonium chloride.
Then run off the lower aqueous layer, and shake the ethereal
solution with about an equal volume of dilute sulphuric acid to
remove traces of foul-smelling phenyl isocyanide (C 6 H 5 NC)
which are always present. Finally separate the sulphuric acid
as completely as possible, and shake the ether with water to
ensure absence of acid. Run off the water and dry the benzo-
nitrile solution over granular calcium chloride for about 20
minutes.
Filter the dried ethereal solution, and then distil off the ether
from a small flask, using precisely similar apparatus and the same
method as those described in the preparation of aniline (Fig. 64,
p. 163; see also Fig. 23(E), p. 45) and observing the same precau-
tions. When the ether has been removed, fit the distilling-flask
to a short air-condenser, and distil the benzonitrile, collecting
the fraction boiling between 187° and 191°. Yield, 16-5 g. (16 ml.).
Benzonitrile is a colourless liquid, having b.p. 190° and d,
1-02: it is almost insoluble in water, and has an odour resembling
that of nitrobenzene and of benzaldehyde.
Hydrolysis of Benzonitrile. Benzonitrile is moderately readily hydro-
lysed by 10% aqueous sodium hydroxide, but only slowly by hydrochloric acid
(cf. p. 122). Ready hydrolysis is obtained by boiling the nitrile under reflux
C 6 H 6 CN + 2H 2 O = C6H5COOH + NH 8
PREPARATIONS I 93
with 70% sulphuric acid (preparation, p. 109), but the benzoic acid volatilises
in the steam and crystallises again in the reflux condenser, which may become
choked with a hard deposit of the acid: moreover some aromatic nitriles are
liable to undergo sulphonation as well as hydrolysis when boiled with such
concentrated sulphuric acid. These disadvantages do not apply to hydrolysis
by sodium hydroxide, as the benzoic acid remains in solution as sodium benzo
ate: furthermore, the completion of the hydrolysis is readily detected by the
complete disappearance of oily drops of the insoluble nitrile.

Boil 5 ml. (5-1 g.) of benzonitrile and 75 ml. of 10% aqueous


sodium hydroxide in a 200 ml. flask under a reflux water-condenser
until no more oily drops of unchanged nitrile run down from the
condenser (usually about 40 minutes). Then detach the condenser
and boil the solution in the open flask for a few minutes to remove free
ammonia, Cool the liquid, and add concentrated hydrochloric acid
cautiously until precipitation of benzoic acid is complete. Cool the
mixture again thoroughly, filter off the benzoic acid at the pump, and
wash well with cold water. Yield, 5-8 g. (almost theoretical).
Confirm the identity of the benzoic acid by the tests given on p. 347.
The benzoic acid obtained in this way should be pure and have m.p.
121°: a portion may if desired be recrystallised from hot water.
Benzamide from Benzonitrile. (A) Although benzonitrile when boiled with
70% sulphuric acid undergoes ready hydrolysis to benzoic acid (see above),
treatment with hot 90% sulphuric acid gives the intermediate benzamide. This
difference arises partly from the difference in temperature employed, but also

C 6 H 3 -C = N->[C,H6-C
OH
from the fact that the speed of hydrolysis of a nitrile to an amide increases
rapidly and steadily with the concentration of the acid, whereas the speed of
hydrolysis of the amide to the acid rises to a maximum and then decreases.
(B). Many nitriles when treated with hydrogen peroxide in warm alkaline
solution undergo hydrolysis to amides which can thus be readily obtained in
high yield. Insoluble liquid nitriles can be treated directly in the aqueous sus-
pension, but for insoluble solid nitriles the addition of a suitable organic solvent
to give a complete solution may be desirable, although the completion of the
hydrolysis may not then be so readily detected.
This method has the great advantage over method (A) in that it can be
applied in particular to those aromatic nitriles in which the aryl group is readily
sulphonated: clearly, it can also be applied to nitriles in which the alkyl or aryl
portion contains groups which are in any other way affected by concentrated
sulphuric acid, or by concentrated aqueous alkalis.
Method A. Prepare approximately 90% sulphuric acid by adding
25 ml. of the concentrated acid cautiously with gentle shaking to 5 ml.
of water.
Add 2 g. (2 ml.) of benzonitrile to 20 ml. of 90% sulphuric acid in a
194 PRACTICAL ORGANIC CHEMISTRY
conical flask: a clear solution is rapidly obtained. Heat the solution in
an oil-bath at 120-130° for 20 minutes, and then cool the solution and
pour it on to 50 g. of crushed ice. Filter the precipitated benzamide at
the pump, wash it with water, and recrystallise it once (or twice) from
water. The benzamide is obtained as white crystals, m.p. 128-130°.
Yield, i g.
Method(B). Add 3 g. (3 ml.) of benzonitrile to 50 ml. of "io-volum.es"
hydrogen peroxide in a beaker, stir mechanically and add i ml. of 10%
aqueous sodium hydroxide solution. Warm the stirred mixture at 40°
until the oily suspension of the nitrile has been completely replaced by
the crystalline benzamide (45-60 minutes). Cool the solution until
crystallisation of the benzamide is complete, and then filter at the pump
and recrystallise as above. One recrystallisation gives the pure benza-
mide, m.p. 129-130°; yield of purified material, 2-2*5 £•
p-Tolunitrile (/>-Tolyl Cyanide). CH8C9H4CN. (Sand-
meyer's Method.)
Required: />-Toluidine, 24 g.; hydrochloric acid, 55 ml.; sodium
nitrite, 17 g.
The preparation of p-tolunitrile illustrates the method employed for
the diazotisation of amines the hydrochlorides of which are only moder-
ately soluble in cold water. Dissolve 24 g. of powdered p-toluidine in
a warm mixture of 55 ml. of concentrated hydrochloric acid and 180 ml.
of water, and then chill the solution thoroughly in ice-water: during the
cooling, stir the mixture continuously in order to ensure that the p-
toluidine hydrochloride crystallises out as small feathery crystals which
will subsequently redissolve readily during the diazotisation. Now
continue precisely as in the above preparation of benzonitrile (p. 191),
observing the same precautions against inhaling cyanogen, and using the same
quantities of all the reagents, i.e.9 diazotising with a solution of 17 g.
of sodium nitrite in 40 ml. of water, and pouring the diazotised so-
lution into the potassium cupro-cyanide solution prepared as before.
During the addition of the diazotised solution, however, the potassium
cupro-cyanide mixture must be occasionally warmed on a water-bath
in the fume-cupboard in order to keep the temperature between 6o°
and 70°.
If during the steam-distillation the p-tolunitrile tends to crystallise
in the condenser, it is usually sufficient to increase the amount of steam
momentarily in order to melt and dislodge the nitrile: alternatively
the condenser-water can be turned off for a few moments. Collect
about 500 ml. of distillate to ensure complete distillation of the nitrile,
and cool the receiver in ice-water during the distillation. The oily
nitrile in the distillate readily solidifies, particularly on stirring. Then
filter at the pump, and press and drain the solid nitrile thoroughly on
the filter to remove liquid impurities. Dry in a desiccator, or by press-
ing between layers of drying-paper: in the latter case, take care that the
PREPARATIONS !95
nitrile does not melt under the warmth of the hand. p-Tolunitrile is
thus obtained as a pale brown solid: yield, 19 g. Purify the dry
material by direct distillation, preferably after mixing it with 1-2 g.
of animal charcoal: use a short air-condenser, which will require
gentle warming at the beginning of the distillation to prevent premature
crystallisation. Collect the fraction having b.p. 214-218°. The distilled
nitrile solidifies as colourless crystals, m.p. 29°, b.p. 218°.
Hydrolysis of />-Tolunitrile. As in the case of benzonitrile,
alkaline hydrolysis is preferable to hydrolysis by 70% sulphuric acid.
Boil a mixture of 5 g. of p-tolunitrile, 75 ml. of 10% aqueous sodium
hydroxide solution and 15 ml. of ethanol under a reflux water-condenser.
The ethanol is added partly to increase the speed of the hydrolysis,
but in particular to prevent the nitrile (which volatilises in the steam)
from actually crystallising in the condenser. The solution becomes clear
after about i hour's heating, but the boiling should be continued for a
total period of 1-5 hours to ensure complete hydrolysis. Then pre-
cipitate and isolate the p-toluic acid, CH3C6H4COOH, in precisely the
same way as the benzoic acid in the above hydrolysis of benzonitrile.
Yield 5-5 g. (almost theoretical). The p-toluic acid has m.p. 178°,
and may be recrystallised from a mixture of equal volumes of water and
rectified spirit.
The methyl group in />-toluic acid may be oxidised to a - COOH group
forming />-phthalic (or tere-phthalic) acid, C 6 H 4 (COOH) 8 , but the oxidation is
usually slow.

Phenol. C1H5OH.
When a diazoniurn salt in aqueous solution is gently warmed, it reacts with
the water, liberating nitrogen and forming the corresponding phenol:
C 6 H 5 N 2 HSO 4 + HOH -> C 6 H 5 OH + N 2 -f H 2 SO 4
The diazoniurn hydrogen sulphate is used for this reaction in preference to the
diazonium chloride since the latter by direct decomposition always forms small
quantities of the chloro-hydrocarbon as a by-product:
C 8 H 5 N 2 Cl = C 6 H 5 Cl + N 3
For the preparation of phenol, the aqueous solution should be heated carefully
to 50-55°, at which temperature the reaction proceeds smoothly: above this
temperature, however, the reaction may rapidly become very vigorous, and
the heat of reaction will then cause a marked rise in the temperature and the
production of a large amount of tarry byproducts.
Required: Sulphuric acid, 27-5 ml.; aniline, 24 ml.; sodium
nitrite, 20 g.; dry potassium carbonate, 3-4 g. (To ensure that
the potassium carbonate is dry, it should be gently heated in an
evaporating-basin over a small Bunsen flame for 4-5 minutes
with stirring, and then allowed to cool in a desiccator.)
Add 27-5 ml. (50-5 g.) of concentrated sulphuric acid cau-
196 PRACTICAL ORGANIC CHEMISTRY
tiously with shaking to 150 ml. of water, and to the hot solution so
obtained, add 24 mi. (24-5 g.) of aniline. If all the aniline
sulphate thus formed does not dissolve, warm the mixture gently
until a clear solution is obtained. Now pour the solution into
200 ml. of cold water contained in a 600 ml. flask, and cool the
mixture in ice-water until the temperature falls to 5°. (Some
aniline sulphate may crystallise out again at this stage. This
does not interfere with the reaction, however, because the sul-
phate separates as very fine crystals which rapidly redissolve
as the reaction proceeds.) Dissolve 20 g. of sodium nitrite in
50 ml. of water, and add this cautiously to the aniline sulphate
solution, carrying out the diazotisation with the precautions
described in the preparation of iodobenzene (p. 184). When all
the sodium nitrite solution has been added, allow the solution to
stand at room temperature for 15 minutes to ensure complete
diazotisation, and then place the flask in a water-bath and heat the
latter until the temperature of the diazotised solution (recorded by
a thermometer in the solution itself) reaches 50-55°. Continue
the heating for a further 30 minutes, taking particular care that
the temperature of the well-stirred solution does not rise above 55°.
A vigorous evolution of nitrogen occurs meanwhile, and the liquid
becomes dark in colour. Pour the contents of the flask into a
i-litre round-bottomed flask, and steam-distil, collecting about
500 ml. of distillate: the solution is apt to foam during the steam
distillation, hence the necessity for the large flask.
Now transfer the cold distillate to a separating-funnel,* and
shake vigorously with about 50-60 ml. of ether: run off the
lower aqueous layer and then decantf the ethereal solution
through the mouth of the funnel into a 200 ml. conical flask.
Replace the aqueous layer in the funnel, and extract similarly
twice more with ether, combining the ethereal extracts in the
conical flask. Add 3-4 g. of dry powdered potassium car-
bonate to the ethereal solution, securely cork the flask and
shake the contents gently. The ethereal solution of the phenol
* If only small separating-funnels are available, divide the distillate into
portions, and extract each thoroughly with ether, uniting the ethereal extracts
subsequently.
t The ethereal solution is decanted through the mouth of the funnel to
prevent contamination by traces of water which, after running off the heavier
aqueous layer, will always be present in the tap and the stem of the funnel.
Traces of water will similarly still be present also in the body of the separating-
funnel, but will remain adhering to the sides when the ethereal solution is
carefully decanted through the mouth. This process should be generally
adopted for removing a light liquid from a separating-funnel after a heavier
liquid has been run off.
PREPARATIONS I97
should now be allowed to remain in contact with the potassium
carbonate for at least one hour, and preferably overnight.
Then fit up the apparatus for ether distillation as shown
in Fig. 64 (p. 163, or Fig. 23(E), p. 45). Filter the dry ethereal
solution through a small fluted filter-paper directly into the
dropping-funnel, run about 30 ml. into the distilling-flask, and
finally continue running in the solution as fast as the ether distils
over (as described in the preparation of aniline, p. 164). When all
the ether has apparently distilled off, disconnect the flask, and
fit it with a thermometer reading up to at least 200°, and also
with an air-condenser about 12-14 inches long. Now heat the
flask very cautiously, as some residual ether always comes over
at first, although the temperature may rise rapidly above the
boiling-point of ether itself: therefore keep flames away from the
open end of the condenser, particularly during the early stages of
the distillation. Distil the phenol at such a rate that none escapes
condensation, and none crystallises in the condenser. Finally
collect the fraction boiling at 178-184° directly into a small
weighed specimen-tube, where it should crystallise on cooling.
The phenol so obtained sometimes remains as a super-cooled
liquid which does not readily crystallise: in such a case, chill the
liquid in ice-water, and either scratch it with a glass rod, or seed
it with a crystal of pure phenol, when crystallisation should
rapidly occur. Yield, 14 g.
Pure phenol is a colourless crystalline substance, having m.p.
43°, and b.p. 182°: on exposure to air, it slowly sublimes, and
on exposure to light, develops a pink colour. It has a character-
istic odour, and a limited solubility in water. Phenol in dilute
aqueous solution has strongly antiseptic properties, but the crys-
talline substance should not be allowed to come in contact with
the skin, as it may cause severe blistering.
For reactions of phenol, see p. 337.

Phenylhydrazine. C9H6NH NH1.


Benzenediazonium chloride reacts in solution with sodium sulphite to give
benzenediazonium sodium sulphonate, which when treated with sulphurous
acid undergoes reduction to phenylhydrazine sodium sulphonate. The latter
readily hydrolyses in the presence of concentrated hydrochloric acid to give
C6H6N1Cl + Na8SO, = C6H5N3SO8Na + NaCl
C6H5N1SO8Na + zH = C.H5NH-NH SO8Na
C 6 H 6 NH-NH-SO 3 Na + HCl + H,O = C 6 H 6 NH NH,,HC1 + NaHSO4
phenylhydrazine hydrochloride, from which the free base can be isolated by the
198 PRACTICAL ORGANIC CHEMISTRY
action of sodium hydroxide solution.
Benzenediazonium chloride also undergoes direct reduction to phenylhydrazine
C 6 H 5 N 2 Cl -f 2SnCl2 + 4HC1 = C,H 6 NH-NH 2 ,HC1 -f
when treated with an acid solution of stannous chloride (e.g., a solution in
hydrochloric acid) but the yields are not as high as those obtained by the above
sulphonate method.
Required: Aniline, 20 ml.; hydrochloric acid, 50 ml.; sodium
nitrite, 17 g.; sodium carbonate (anhydrous) 17 g.; sodium
sulphite (7H2O), 115 g
First prepare a solution of benzenediazonium chloride from 20
ml. (20-5 g.) of aniline precisely as described in the preparation
of chlorobenzene (p. 189), adding a solution of 17 g. of sodium
nitrite in 40 ml. of water to a solution of the aniline in 50 ml. of
concentrated hydrochloric acid and 50 ml. of water, the tempera-
ture of the mixture being kept between 5° and 10°.
While this solution is standing, dissolve 17 g. of anhydrous
sodium carbonate in 70 ml. of warm water in a 8oo ml. beaker, and
then add 115 g. of finely powdered crystalline sodium sulphite
(Na 2 SO 3 JH 2 O) and continue warming the solution at 40-50° for
a few minutes, so that the greater part of the sulphite dissolves.
Then cool the solution in ice-water until the temperature is be-
tween 5° and 10°, some of the sulphite meanwhile crystallising out
again. Now add the diazonium solution slowly to the well-stirred
sulphite solution: the mixture becomes red in colour, and a deep
red oil separates and later solidifies as orange-coloured crystals
(sometimes the orange crystals separate without the intermediate
formation of the oil). When the addition of the diazo solution is
complete, continue stirring the mixture for 5-10 minutes, and then
warm it to 30° on a water-bath (in a fume-cupboard) and pass in
a stream of sulphur dioxide from a syphon until the solution is
saturated and no more gas is absorbed: the excess of sodium
sulphite and the orange crystals dissolve up at this stage. Now
heat the solution to 70° and add 150 ml. of concentrated hydro-
chloric acid with stirring. Within a few minutes, crystals of
phenylhydrazine hydrochloride separate out: cool the mixture in
ice-water for 15 minutes with occasional stirring and then filter
at the pump and drain thoroughly.
Suspend the crude hydrochloride in some water in a separatmg-
funnel and add 20% sodium hydroxide solution until the mixture
is definitely alkaline and the crude phenylhydrazine base floats as
a deep red oil on the surface. Now extract the phenylhydrazine
twice with benzene (using about 30 ml. of benzene on each
occasion) and dry the united benzene extracts with powdered
PREPARATIONS 199
anhydrous potassium carbonate. After the mixture has been
allowed to stand for 20-30 minutes, filter at the pump, and wash
the residual carbonate with a small quantity of dry benzene.
The benzene has now to be distilled off at atmospheric pressure
and the residual phenylhydrazine at reduced pressure. For this
purpose, fit a small dropping-funnel to the main neck of a 6o ml.
Claisen flask, cork the other neck, and fit a water-condenser to
the side-arm. Run about 30 ml. of the benzene solution into the
flask, and heat the latter in an oil-bath, controlling the tempera-
ture of the bath so that the benzene distils gently over. Allow the
remainder of the solution to run in from the dropping-funnel as
fast as the benzene itself distils over. When the benzene has been
almost entirely removed, fit a capillary tube and a thermometer
into the necks of the flask, and then assemble the complete
apparatus for vacuum distillation, using either the simple
apparatus shown in Fig. IZ(A) (p. 29) or a water-condenser fitted
with a "pig" (Fig. 13, p. 31, or Fig. 23(F), p. 46). Distil the
phenylhydrazine carefully from an oil-bath and collect a fraction
boiling over a range of about 3°, e.g., at 127-130°/22 mm. The
phenylhydrazine is thus obtained as a very pale yellow (almost
colourless) oil, of d, 1*10: it has a characteristic odour and is only
slightly soluble in water. Yield, 16-17 g. Pure phenylhydrazine
has m.p. 23°; it boils at 242-243° at atmospheric pressure with
partial decomposition.
Phenylhydrazine on exposure to light slowly darkens and eventually
becomes deep red in colour: salts of the base share this property but
to a lesser degree, the sulphate and acetate (of the common salts) being
most stable to light. Phenylhydrazine is largely used in organic
chemistry to characterise aldehydes and ketones as their phenyl-
hydrazones (pp. 342, 345), and carbohydrates as their osazones (pp.
136-140). It is readily reduced: thus in the process of osazone formation
some of the phenylhydrazine is reduced to aniline and ammonia. On the
C 6 H 5 NH-NH 2 + 2H = C 6 H 5 NH 2 + NH3
C 6 H 5 NH-NH 2 + 2CuO = C 6 H 6 + N 2 + Cu2O + H2O
other hand, Fehling's solution oxidises it to benzene and nitrogen.
Add 2-3 drops of phenylhydrazine to about 2 ml. of Fehling's solution
in a test-tube and shake the mixture vigorously: nitrogen is evolved and
reddish-brown cuprous oxide is precipitated. The reaction proceeds
rapidly on gentle warming, more slowly in the cold.
Biphenic Acid.* C12H8(COOH)2.
Many diazonium compounds when treated with an ammoniacal cuprous
* Formerly known as Diphenic acid.
200 PRACTICAL ORGANIC CHEMISTRY
solution undergo loss of nitrogen with the formation of the corresponding
biphenyl derivative. The yield depends largely on the diazotised amine
employed, but anthranilic acid (I) gives biphenic acid ( I I I ) or (biphenyl-
2,2'-dicarboxylic acid) in high yield. The reaction may often be promoted by
COOH
rCOOH
1-NH2 ^ JJ-N 2 Cl
COOH
(IU)

cuprous chloride, but this reagent tends to contaminate the product with the
chloro-compound corresponding to the amine employed (Sandmeyer's reaction,
p. 189).
Required: Anthranilic acid, 20 g. anhydrous sodium car-
bonate, 7-5 g.; sodium nitrite, 12 g.; concentrated hydrochloric
acid, 190 ml.; crystalline copper sulphate, 50 g.; concentrated
ammonia, 85 ml.; hydroxylamine hydrochloride, 14-5 g. (or
hydroxylamine sulphate, 17-4 g.); acetic acid, 10-20 ml.
(A) Diazotisation of Anthranilic Acid. Dissolve 20 g. of
anthranilic acid in a solution of 7-5 g. of anhydrous sodium car-
bonate in 200 ml. of water contained in a 400 ml. beaker. (The
mixture may be warmed very gently with stirring to obtain a
solution more rapidly, and then cooled.) Add slowly 12 g. of
sodium nitrite and cool the stirred solution below 10°. Pour this
cold solution slowly on to a vigorously stirred mixture of 40 ml.
of concentrated hydrochloric acid and 120 g. of crushed ice in a
600 ml. beaker.
(B) Preparation of the Cuprous Solution. Add 85 ml. of con-
centrated ammonia solution (d, 0-088) to a solution of 50 g. of
crystalline copper sulphate in 200 ml. of water, and cool to 10°.
Dissolve 14-5 g. of hydroxylamine hydrochloride (or 17-4 g. of
the sulphate) in 50 ml. of water, cool to 10°, and add a solution
of 9 g. of sodium hydroxide in 30 ml. of water. Without delay >
add this hydroxylamine solution with stirring to the copper
solution, which will be immediately reduced, but will retain a
blue colour.
Place the cuprous solution in a 1200 ml. beaker, and cool it in
ice-water with (mechanical) stirring: run in the diazotised
solution slowly from a dropping-funnel, keeping the temperature
below 10° throughout. When the addition of the diazotised
solution is complete, heat the reaction-mixture rapidly to boiling
and then slowly add 150 ml. of concentrated hydrochloric acid.
The biphenic acid separates as a pale brown crystalline deposit.
PREPARATIONS 201
Set aside (preferably overnight), and then filter off the acid,
wash it with water and dry. Yield of crude acid, 12 g.; m.p.
223-226°.
For purification, transfer the acid to a 150 ml. flask containing
60 ml. of water, boil the mixture under reflux, and then add
acetic acid in 5 ml. portions down the condenser until almost all
the solid has dissolved: avoid an excess of acetic acid by ensuring
that the solvent action of each addition is complete before the
next portion is added. A small suspension of insoluble impurity
may remain. Add 2 g. of animal charcoal, boil the solution
again for 10-15 minutes, and then filter it through a preheated
Buchner funnel. Cool and stir the filtrate, which will deposit
pale cream-coloured crystals of the acid. Collect as before and if
necessary repeat the recrystallisation. Yield of pure acid, 9 g.;
m.p. 227-229°.
4(or />)-Bromobiphenyl. BrC6H4-C6H5. (Gomberg Re-
action.)
When an aqueous solution of a diazonium salt is added to an alkaline solution
of a phenol, coupling occurs with formation of an azo-compound (p. 188).
If however the aqueous solution of the diazonium salt, e.g., />-bromobcnzenc
diazonium chloride, is mixed with an excess of an aromatic hydrocarbon, and
aqueous sodium hydroxide then added to the vigorously stirred mixture, the
diazotate which is formed, e.g., BrC 6 H 4 N 2 OH, dissolves in the hydrocarbon
and there undergoes decomposition with the formation of nitrogen and two
free radicals. The aryl free radical then reacts with the hydrocarbon to give a
biphenyl. • •
BrC 6 H 4 N 2 OH -> BrC 6 H 1 + N 2 + OH
BrC8H4 + C8H9 + OH -+ BrC6H4-C8H8 -f H1O
The free radical mechanism is confirmed by the fact that if a substituted
aromatic hydrocarbon is used in this reaction, the incoming group (derived
from the diazotate) may not necessarily occupy the position in the benzene
ring normally determined by the substituent present—a characteristic of free
radical reactions.
Required: p-Bromoaniline, 20 g.; benzene, 150 ml.; sodium nitrite,
8
*5 g-
Add 20 g. of />-bromoaniline to 20 ml. of water in a 250 ml. beaker,
and warm the mixture until the amine melts. Now add 23 ml. of
concentrated hydrochloric acid and without delay stir the mixture
mechanically in an ice-water bath, so that a paste of fine p-bromo-
aniline hydrochloride crystals separates. Maintain the temperature
of the stirred mixture at about 5° whilst slowly adding from a dropping-
funnel a solution of 8-5 g. of sodium nitrite in 20 ml. of water: con-
tinue the stirring for 20 minutes after the complete addition of the
nitrite.
202 PRACTICAL ORGANIC CHEMISTRY
Transfer the diazotised solution, to a 600 ml. beaker, add 150 ml. of
benzene, and stir the mixture vigorously to obtain an intimate mixture
of the two liquids. Then again maintain the temperature at about 5°
(by ice-salt cooling because of the heat evolved) whilst 27 ml. of 20%
aqueous sodium hydroxide solution are added from a dropping-funnel
during 40-50 minutes. When the addition of the alkali is complete,
remove the ice-water bath, and allow the stirred mixture to reach room
temperature.
Pour the mixture into a 500 ml. flask fitted with a steam-distillation
head, and with a steam-inlet tube reaching almost to the bottom of the
flask. First distil of! the benzene in steam. Then place the flask in an
oil-bath heated to 165-170°, and continue the steam-distillation (2-3
hours). The p-bromobiphenyl passes over and forms orange crystals in
the water-condenser: therefore run the water out of the condenser for a
short while from time to time to melt the orange deposit and allow it to
run into the receiver containing the distilled water.
When the distillation is complete, filter oil the crude orange solid
(9 g.) at the pump, wash it with water and drain well. Recrystallise
from methanol or from methylated spirits. The p-bromobiphenyl is
obtained as colourless lustrous plates, m.p. 89-91°: yield, 7 g.

1,3,5-Tribromobenzene, C 6 H 3 Br 35 from 254,6-Tribromo-


aniline.
When a solution of a diazonium compound in absolute methanol is boiled,
the chief product is the corresponding methyl ether, benzenediazonium hydro-
gen sulphate thus giving methyl phenyl ether or anisole:
C^H 5 N 2 HSO 4 + HOCH3 - C 9 H 6 OCH 3 + N 2 + H 2 SO 4
In absolute ethanol solution, the ethyl ether and the corresponding hydro-
carbon are formed, the latter by reduction of the diazonium compound by the
ethanol, which is itself oxidised to acetaldehyde:
CH 3 CH 2 OH = CH 3 CHO + aH
C 6 H 5 N 2 HSO 4 4-2H = C 6 H 6 + N 2 + H 2 SO 4
With higher alcohols, the formation of the ether becomes negligible, the
reaction being limited almost entirely to reduction to the hydrocarbon.
This elimination of the diazonium group is therefore a very valuable re-
action, as it affords almost the only method by which nitro and primary
amino groups directly attached to the benzene ring can be eliminated.
A similar reaction occurs when an aqueous solution of a diazonium compound
is made strongly alkaline and then warmed with an alkaline solution of stannoqs
chloride. This reaction, however, involves the intermediate formation of the
KOH 2H
C 6 H 6 N 2 Cl > C 4 H 6 NiNOK > C9H9 + N, -f KOH
unstable alkali diazotate, which may explode even in cold aqueous solution.
2,4,6-Tribromoaniline (preparation, p. 165) is used to illustrate this
PREPARATIONS 203
elimination of the amino group, because the tribromobenzene so formed
is solid, and small quantities can easily be purified by recrystallisation.
Required: 2,4,6-Tribromoaniline, 5 g.; absolute ethanol, 40 ml.;
dry benzene, 10 ml.; sodium nitrite, 3 g.
Dissolve 5 g. of 2,4,6-tribromoanilinc in a hot mixture of
40 ml. of absolute ethanol and 10 ml. of dry benzene con-
tained in a 150 ml. wide-necked bolt-head flask. (The benzene
is added to increase the solubility of the tribromoaniline.)
Now add 2 ml. (3-9 g.) of concentrated sulphuric acid (pre-
ferably from a burette or a small pipette) to the hot solution,
shaking the latter gently round. Attach the flask to a reflux
water-condenser and heat on a water-bath until the clear solution
boils. Now detach the flask, add 3 g. of dry powdered sodium
nitrite, and return the flask to the condenser but not to the water-
bath. Shake the flask vigorously: the heat of the reaction causes
the solution to continue boiling for several minutes. When the
boiling subsides, return the flask to the water-bath and boil the
solution for 45 minutes with occasional vigorous shaking. Allow
the solution to cool somewhat and then cool it thoroughly in ice-
water. A mixture of tribromobenzene and sodium sulphate
crystallises out. Filter at the pump, drain, wash once with a small
quantity of methylated or rectified spirit and then repeatedly
with water to remove all sodium suplhate.
Recrystallise from methylated spirit, using animal charcoal:
for this purpose, use about twice the minimum quantity of
methylated spirit required to obtain a clear solution, and filter
through a funnel preheated by the filtration of some boiling
solvent, as the tribromobenzene separates very rapidly as the
solution cools. The 1,3,5-tribromobenzene is thus obtained as
colourless crystals, m.p. 122°: yield, 3 g.
The tribromobenzene obtained in this way should be entirely free from
unchanged tribromoaniline. To test its purity, dissolve a small quantity in
hot dry benzene and pass in hydrogen chloride gas from a Kipp's appar-
atus: no trace of crystals of tribromoaniline hydrochloride should appear.
Note also that although the m.p.s of the two compounds are almost identical,
that of the recrystallised product from the above preparation is considerably
depressed by admixture with tribromoaniline.
Diphenylnitrosoamine.* (C0H.-,) 2 N«NO. (Semi-micro
scale.)
Secondary amines of both the aliphatic and the aromatic series react similarly
with nitrous acid, giving nitrosamines:
* Alternative name A r -nitrosodiphenylamine.
204 PRACTICAL ORGANIC CHEMISTRY
R 2 NH + HONO -> R 2 N-NO + H 2 O
The nitrosamines are insoluble in water, and the lower members are liquid at
ordinary temperatures. The separation of an oily liquid when an aqueous
solution of an amine salt is treated with sodium nitrite is therefore strong
evidence that the amine is secondary. Diphenylnitrosoamine is selected as a
preparation because it is a crystalline substance and is thus easier to manipu-
late on a small scale than one of the lower liquid members. For this pre-
paration, a fairly pure (and therefore almost colourless) sample of diphenyl-
amine should be used. "Technical" diphenylamine, which is almost black in
colour, should not be employed.
Required: Diphenylamine, i g.; ethanol, 8 ml.; sodium nitrite,
°'S g-> hydrochloric acid, 0-8 ml.
Prepare two solutions, one containing i g. of diphenylamine
in 8 ml. of warm ethanol, and the other containing 0-5 g. of
sodium nitrite in i ml. of water, and cool each solution in ice-
water until the temperature falls to 5°. Now add 0-8 ml. of con-
centrated hydrochloric acid steadily with stirring to the diphenyl-
amine solution, and then without delay (otherwise diphenylamine
hydrochloride may crystallise out) pour the sodium nitrite
solution rapidly into the well-stirred mixture. The temperature
rises at once and the diphenylnitrosoamine rapidly crystallises
out. Allow the mixture to stand in the ice-water tor 15 minutes,
and then filter off the crystals at the pump, drain thoroughly,
wash with water to remove sodium chloride, and then drain
again. Recrystallise from methylated spirit. Diphenylnitroso-
amine is thus obtained as very pale yellow crystals, m.p. 67-
68°: yield, 0-9-1 -o g.
Reaction of Diphenylnitrosoamine. Carry out Liebermann's Nitroso
Reaction as described for phenol (p. 340), but use about 0-05 g.
of the nitrosamine instead of the one crystal of sodium nitrite, and
finally add only 3-4 drops of sulphuric acid. The deep greenish-blue
colour is obtained, becoming red on dilution and reverting to blue on
being made alkaline.

/>-Nitrosodimethylaniline.t (CH 3 )JVC 6 H 4 NO.


Nitrous acid does not react with aliphatic tertiary amines, such as triethyl-
amine, (C,H 6 ) 8 N, nor does it usually react with aromatic tertiary amines such
as triphenylamine, (C«H 6 ) 3 N, which contain three aryl groups.
If, however, a tertiary amine has two alkyl groups and also an aryl group
having the para position unsubstituted, then the action of nitrous acid is to
insert the nitroso group directly into this para position. Dimethylaniline, for
example, when treated with nitrous acid readily gives />-nitrosodimethyl-
f Alternative name Ar,A^'-dimethyl-/)-nitrosoaniline.
PREPARATIONS 205
(CH 3 ),NC«H 5 HOXO — (CH 3 ) 2 NC 6 H 4 NO : H 2 O
aniline. The salts of />-nitrosodimethylaniline, such as the hydrochloride, are
yellow, whereas the free base is a beautiful green crystalline compound. The
colouris presumably dueto a strong contribution by the quinonoid form in which
a charge separation has occurred within the molecule:

0IN-C 6 H 4 -N(CH 8 ), «-* 6-N:CeH 4 :N(CH,) t


This marked difference in colour between a base and its salts is also exemplified
in the case of ammouzobenzene (p. 208).
Tertiary amines containing one alkyl and two aryl groups, such as mono-
r.iethykliphenylaminc, CI I : i (C ( i H 5 ) 2 N, are rarely encountered and arc unim-
portant. They usually react with nitrous acid with the insertion of a nitroso
group into only one of the two available para positions: monomethyl-
diphenylamine thus gives monomethyl -mono -/>- nitroso - diphenylamine,
Cl I 3 (C ,.,H ,)NC<;H 4 XO, or A'-methyl-/>-nitrosodiphenylamine.
Required: Dimethylaniline, 15 ml.; hydrochloric acid, 50 ml.;
sodium nitrite, 9 g.
Dissolve 15 ml. (14-3 g.) of dimethylaniline in a mixture of
50 ml. of concentrated hydrochloric acid and 50 ml. of water
contained in a 300 ml. beaker, and then place the latter in a
freezing-mixture consisting of finely crushed ice and salt. Stir
the contents of the beaker with a thermometer until the tempera-
ture of the solution is between o° and 2°. Dissolve 9 g. of sodium
nitrite in 20 ml. of water and add this solution in small quantities
(about 2 ml. at a time) to the dimethylaniline hydrochloride
solution, keeping the mixture well stirred and taking care that the
temperature recorded by the thermometer in the solution does
not rise above 2°. When the addition of the sodium nitrite
solution is complete, allow the product to remain in the freezing-
mixture for a further 45 minutes, and then filter off the yellow
crystalline nitrosodimethylaniline hydrochloride at the pump,
wash it with dilute hydrochloric acid, and then drain thoroughly.
Yield of crude hydrochloride, about 18 g. Recrystallise approx-
imately half the hydrochloride by dissolving it in a minimum
amount of boiling water, and adding about 0-5 ml. of concentrated
hydrochloric acid: on cooling the solution, the hydrochloride
crystallises out in yellow needles, m.p. 177°.
In order to prepare the free base, place the remaining half of
the crude hydrochloride in a 200 ml. beaker, add 20 ml. of water,
and then stir the mixture with a glass rod until a thin paste of
uniform consistency (quite free from lumps) is obtained. Now
add io % aqueous sodium hydroxide solution with stirring until
the whole mass has become bright green—the colour of the free
206 PRACTICAL ORGANIC CHEMISTRY
base. Pour the contents of the beaker into a separating-funnel,
and isolate the free base by one of the following alternative
methods.
(a) Extract the free base by shaking the mixture in the separating-
funnel with about 40 ml. of benzene, repeating the extraction to
ensure that all the base has entered the benzene solution. Dry the
combined benzene extracts by shaking with powdered anhydrous
potassium carbonate for a few minutes, and then filter through a
fluted filter-paper directly into a distilling-flask fitted with a
water-condenser. Distil off about half the benzene over a sand-
bath, and then pour the residual hot benzene solution into a small
beaker. On cooling, the />-nitrosodimethylaniline crystallises
out in brilliant deep green leaflets: when these are filtered off
and dried, however, they usually decrepitate, giving a fine green
crystalline powder, m.p. 85°.
(b) Extract the mixture with about 40 ml. of chloroform, in
which the free base is very soluble. Run off the lower chloroform
layer, dry it with potassium carbonate as in (a), and then add
carbon tetrachloride slowly with stirring to the filtered chloroform
solution until the base starts to crystallise out. Allow to stand for
a short time (i.e., until the deposition of crystals ceases) and then
filter at the pump: as the crystals lose the last trace of solvent,
they tend as before to break up into a fine powder, the deep green
colour becoming paler in consequence.
A small quantity of the base may be recrystallised from hot
ether, and magnificent deep green crystals obtained: the base is
not sufficiently soluble in cold ether, however, to enable this
solvent to be used advantageously in the above extractions.
Reactions, (i) p-Nitrosodimethylaniline does not give Liebermann's
Nitroso Reaction with phenol and sulphuric acid (see footnote, p. 340).
(2) Place about i g. of the base in a test-tube, and cover with con-
centrated (about 20%) sodium hydroxide solution. Bring the mixture
gently to the boil, keeping the test-tube lightly closed with the finger
meanwhile to prevent undue escape of vapour. As the solution boils
a strong fishy odour of dimethylamine is detected, and white fumes
form when the test-tube is held near an open bottle of concentrated
NaOH - (CH 3 ) 2 XC 6 H 4 NO -> (CH 3 ) 2 NH -f NaOC 6 H 4 XO
hydrochloric acid. The sodium hydroxide has hydrolysed the base,
giving the volatile dimethylamine, whilst the sodium derivative of
p-nitrosophenol remains in solution. The reaction affords an excellent
method of preparing pure aliphatic secondary amines, particularly when
required completely free from primary and tertiary amines.
PREPARATIONS 207
Diazoaminobenzene. C6H5 -N:N -NH -C 6 H 5 .
Diazonium salts couple readily with aromatic primary amines, giving diazo-
amino compounds. If for instance an aqueous solution of aniline sulphate is
diazotised with a deficiency of nitrous acid, only part of it is converted into
benzenediazonium sulphate and the latter then couples with the unchanged
aniline to give diazoaminobenzene. The reaction is carried out at the opti-
C 6 H 5 NH 2 ,H 2 S0 4 + HONO = C 6 H 6 N 2 HSO 4 + 2H2O
C 6 H 5 N 2 HSO 4 -r HXHC 6 H 5 -> C 6 H 5 -NiN-NH-C 6 H 5 } H 2 SO 4
mum temperature of 30°, for at this temperature coupling takes place readily,
and the diazonium sulphate is used up before it has time to decompose.
Dissolve 2 ml. (3-7 g.) of concentrated sulphuric acid in 350 ml.
of water contained in a 600 ml. beaker, and then add with
stirring 12 ml. (12-3 g.) of aniline. Place the beaker in a water-
bath and heat the latter gently until a thermometer in the solution
records a temperature of 30°. Dissolve 4*5 g. of sodium nitrite
in 15 ml. of water, and add about i ml. of this solution at half-
minute intervals to the solution of aniline sulphate, keeping the
mixture well stirred meanwhile. When the addition of the nitrite
is complete, keep the mixture at 30° for a further 15 minutes: the
diazo-aminobenzene rapidly begins to separate as a yellow crystal-
line mass. Then remove the beaker from the bath, and allow it
to stand for 30 minutes, with occasional stirring. Filter off the
solid material at the pump, using a Buchner funnel, wash re-
peatedly with water, and then drain thoroughly. Finally dry the
diazoaminobenzene by pressing between several sheets of thick
drying-paper. The sample so obtained is sufficiently pure for the
following preparation of aminoazobenzene. Yield of crude
material, 11-12 g. (almost theoretical).
The recrystallisation of diazoaminobenzene has to be performed
with care, as the substance is freely soluble in most liquids and
tends moreover to decompose if its solution is not rapidly cooled.
Place 2 g. of the crude, freshly prepared, well-drained material
in a boiling-tube, add about 15-20 ml. of ethanol and 1-2 drops
of 10% aqueous sodium hydroxide solution, and then heat
rapidly until boiling: if the solution should contain insoluble
impurities, filter through a small fluted paper, and at once cool
the filtrate in ice-water. The diazoaminobenzene should
rapidly crystallise out from the cold and stirred solution: filter
the crystals rapidly at the pump whilst the solution is still cold, as
they tend to redissolve if the solution reaches room temperature.
Diazoaminobenzene is thus obtained as yellow crystals, which
208 PRACTICAL ORGANIC CHEMISTRY
melt at 98°, the molten material decomposing vigorously above
this temperature: the crystalline material darkens on exposure to
light and most specimens are therefore of a yellowish-brown colour.
Aminoazobenzene. C6H5 -N :N • C6H 4 -NH 2.
When diazoaminobenzene is added to a warm aqueous solution of hydro-
chloric acid, it tends to break up into its original components, i.e., to benzene-
diazonium chloride and aniline, and an equilibrium is thus established.
The diazonium chloride and the aniline, however, in addition to recombining
to form diazoaminobenzene, also undergo direct condensation at the />-hydro-
C 6 H 5 N a NHC 6 H 6 +HCl^C 6 H B N 2 CH-H 8 NC 6 H 6 ->C 6 H 6 N:NC fl H 4 NH 2 -fHCl
gen atom of the aniline molecule, giving aminoazobenzenc. Since this re-
action is irreversible, whilst the former is freely reversible, the final result is
the complete conversion of the diazoaminobenzene into the aminoazobenzene.
(The intermediate formation of the benzenediazonium chloride can be demon-
strated by adding dimethylaniline, with which the diazonium chloride couples
preferentially, giving dimethylaminoazobenzene, C 6 H 5 NrNC 6 H 4 N(CH 3 ).,.)
The conversion of the diazoaminobenzene into aminoazobenzene is promoted
by the addition of aniline hydrochloride even more readily than by that of free
hydrochloric acid. The aniline hydrochloride dissociates in solution giving
hydrochloric acid and aniline: the former promotes the formation of the above
equilibrium, and the latter by increasing the active mass of the free aniline
further accelerates the condensation to aminoazobenzene.
Aminoazobenzene is a very weak base, and consequently it will not form
salts with weak organic acids, such as acetic acid, although it will do so with the
strong mineral acids, such as hydrochloric acid. Aminoazobenzene is a yellowish-
brown compound, whilst the hydrochloride is steel blue. The colour of the
latter is presumably due to the addition of the proton to the phenyl-N-atom,
the cation thus having benzenoid and quinonoid forms:
+ +
C 6 H 6 -NHiN-C 6 H 4 -NH 1 ^+ C C H 6 -NH-N:C 6 H 4 :NH 2

Required: Aniline hydrochloride, 4 g.; aniline, 16 ml.; diazo


aminobenzene, 8 g.; acetic acid, 20 ml.
Add 4 g. of aniline hydrochloride to 16 ml. of aniline
contained in a ioo ml. conical flask, and then add 8 g. of
diazoaminobenzene, both the solid components being finely
powdered. Place the flask in a water-bath, and heat the latter
carefully so that the well-stirred mixture is kept at 40° for i hour.
Then remove the flask from the water-bath and allow it to stand
overnight to ensure that the conversion is complete. Then add
about 20 ml. of glacial acetic acid dissolved in the same volume of
water, and stir the mixture well to extract the free aniline in the
form of its soluble acetate. Allow the mixture to stand (with
occasional stirring) for at least 10 minutes, and then filter at the
PREPARATIONS 209
pump and wash well with water.
Aminoazobenzene is freely soluble in methylated spirit,
although insoluble in water. For recrystallisation, therefore,
dissolve the crude substance in boiling methylated spirit, remove
from the water-bath, and then add water drop by drop until the
solution becomes just cloudy owing to the separation of the solute:
replace the solution momentarily on the water-bath until the
cloudiness disappears, and then at once remove the solution, and
allow it to cool slowly. (Alternatively, the crude dry material
can be recrystallised from carbon tetrachloride in the usual
way.) Aminoazobenzene is thus obtained as yellowish-brown
crystals, m.p. 126°: yield, 5 g.
To prepare the hydrochloride, add about i g. of amino-
azobenzene to 200 ml. of dilute hydrochloric acid and boil until
nearly all the solid material has dissolved. Filter hot and allow to
cool slowly. Aminoazobenzene hydrochloride separates as
beautiful steel-blue crystals: filter and dry. If a small quantity
of the powdered hydrochloride is moistened with water and a few
drops of ammonia added, the blue hydrochloride is converted
back to the yellowish-brown base.
Azo-Compounds.
Aminoazobenzene is a member of the large class of azo-compounds, all of
which contain the characteristic grouping, C-NiN-C. Azo-compounds are of
considerable technical importance, as they are all coloured, and the majority
possess considerable stability. They may be prepared by the following methods:
(i) By coupling a diazonium salt with:
(a) A primary amine to give the diazoamino compound, which is then
converted into the isomeric aminoazo compound (as in the above
preparation of aminoazobenzene).
C 6 H 5 N 2 HSO 4 + HNHC 6 H 5 -- > C 6 H 5 N 2 NHC 6 H 5 -- > C 6 H 5 NiNC 6 H 4 NH 2
(6) A tertiary amine, the azo-compound being directly formed. Thus
benzenediazonium sulphate and dimethylaniline give dimethylamino-
azobenzene (p. 188).
C 6 H 5 N 2 HSO 4 + HC 6 H 4 N(CH 3 ) 2 -- > C 6 H 5 N:NC 6 H 4 N(CH 3 ) 2
(c) A phenol in alkaline solution. z-Naphthol dissolved in sodium hydrox-
ide solution this gives benzeneazo-2-naphthol, a scarlet dye.
HO HO
C 6 H 5 N 2 HSO 4 + < -^ C 6 H 5 NiN 3 + H 2 SO 4

(2) The alkaline reduction of an aromatic nitro-compound to give the azoxy


2io PRACTICAL ORGANIC CHEMISTRY
derivative, which is then further reduced to the azo-compound. Nitrobenzene
thus gives first azoxybenzene, and then azobenzene.
2C 6 H 6 NO 8 -> C,H 5 NO:NC 6 H 6 -> C 6 H 5 NtNC 8 H 6
(3) By condensing nitroso derivatives with primary amines. Nitrosobenzene
and aniline, for example, readily give azobenzene. This method is seldom used

C 6 H 5 XO -J- H 2 NC 6 H 5 > C 6 H 5 NiNC 6 Pi 5 + H 2 O


but is of importance in that it establishes clearly the constitution of the azo
grouping.
The most noteworthy reaction of azo-compounds is their behaviour on reduc-
tion. Prolonged reduction first saturates the azo group, giving the hydrazo
derivative (C-NH-NH-C), and then breaks the NH-NH linkage, with the forma-
tion of two primary amine molecules. If method (i) has been employed to
prepare the azo-compound, these two primary amines will therefore be respec-
tively (a) the original amine from which the diazonium salt was prepared, and
(b) the amino derivative of the amine or phenol with which the diazonium salt
was coupled. For example, amino-azobenzene on complete reduction gives
one equivalent of aniline, and one of />-phenylene diamine, NH 2 C 6 H 4 NH 8 ;
benzene-azo-2-naphthol similarly gives one equivalent of aniline and one of
HO HO
C 6 H 6 NrNQ + 4 H = C6H8NH1 +

i-amino-2-naphthol, experimental details for this reduction being given below.


The constitution of an azo-compound (and particularly the position of the
azo group in the molecule) can thus often be determined by identifying the
two primary amines formed on complete reduction.
Benzeneazo-2-naphthol.
C6H5-NrN-C10H6OH [Method i(c)].
Required: Aniline, 4-5 ml.; hydrochloric acid, lO'ml.; sodium
nitrite, 4 g.; 2-naphthol, 7 g.
Dissolve 4-5 ml. of aniline in a mixture of 10 ml. of concen-
trated hydrochloric acid and 20 ml. of water: cool the solution to
5°, and diazotise by the addition of 4 g. of sodium nitrite
dissolved in 20 ml. of water, observing the usual precautions given
on page 181. Dissolve 7 g. of 2-naphthol in 6o ml. of 10%
sodium hydroxide solution contained in a 200 ml. beaker, and cool
this solution to 5° by external cooling, aided by the direct addi-
tion of about 20-30 g. of crushed ice. Now add the diazotised
solution very slowly to the naphthol solution, keeping the latter
well stirred meanwhile: the mixed solutions immediately
develop a deep red colour, and the benzeneazonaphthol should
rapidly separate as red crystals. If the diazonium solution is
added too rapidly, the azo-compound may separate at first as a
PREPARATIONS 211
thick viscous mass, which, however, will crystallise later and may
then be easily broken up with the stirrer. When the addition of
the diazo solution is complete, allow the mixture to stand in an
ice-salt mixture for 30 minutes, with occasional stirring, and then
filter the solution through a Buchner funnel under gentle suction
from the pump: if the above directions have been carefully
followed, filtration should be rapid. Wash the benzeneazo-2-
naphthol well with water, and then drain thoroughly, pressing the
crystals well down on to the filter with a spatula. Recrystallise
one-third of the product from glacial acetic acid, reserving the
remainder for reduction to i-amino-2-naphthol. (The azo-
compound when dry is freely soluble, in acetic acid, but when
moist is only moderately soluble: about 40 ml. of acetic acid are
required for the portion recrystallised as above.) Filter the re-
crystallised material at the pump, wash with a few ml. of ethanol
or methylated spirit to eliminate acetic acid, and dry: yield, 3 g.
Benzeneazo-2-naphthol is obtained as deep red crystals, m.p.
133°. Should further recrystallisation of the dry compound be
required, ethanol is the best solvent.
Hydrochloride of i-amino-2-naphthol (i-amino-2-
hydroxynaphthalene). C10H6(NH2)OH5HCL
Required: Benzeneazo-naphthol from above experiment; methylated
spirit, ioo ml.; stannous chloride, 22 g.; hydrochloric acid, 6o ml.
Add the reserved portion of the unrecrystallised benzeneazo-
naphthol to ioo ml. of methylated spirit contained in a 350 ml. conical
flask and boil gently under reflux until the greater part of the azo-
compound has gone into solution. Meanwhile dissolve 22 g. of
stannous chloride in 60 ml. of concentrated hydrochloric acid (warming
gently, if necessary, to obtain a clear solution), add this solution to
that of the azo-compound, and continue the boiling under reflux for 30
minutes. The azo-compound rapidly dissolves, and is reduced by
the stannous chloride, and after about 20 minutes' boiling, the red
colour disappears and the solution acquires a permanent very pale
brown tint. (If the red colour, instead of disappearing, slowly darkens
to a deep reddish-violet, the stannous chloride is at fault, as the violet
colour usually develops if a stale sample of stannous chloride, particu-
larly one which has been unduly exposed to the air, is employed.)
When the boiling for 30 minutes is complete, decant the solution into a
beaker, and cool in ice-water; the amino-naphthol hydrochloride
separates as fine greyish-white crystals. Filter off at the pump, and
wash the hydrochloride thoroughly with dilute hydrochloric acid, in
which it is almost insoluble. Recrystallise from hot water containing a
few drops of dilute hydrochloric acid; care must be taken that too
much water is not used for this purpose, as the hydrochloride usually
212 PRACTICAL ORGANIC CHEMISTRY
contains traces of a sparingly soluble stannous impurity which should
be left undissolved and removed by filtration from the hot solution.
If the hydrochloride does not crystallise readily from the cold filtrate,
seed the latter with a minute quantity of the crude material, or add a
few more drops of dilute hydrochloric acid. i-Amino-2-naphthol
hydrochloride is thus obtained as fine colourless crystals, which darken
in colour on exposure to light: yield, 3 g.
Azoxybenzene, C6H6NOzNC6H59 and Azobenzene,
C6H5NiNC6H6. (Method 2, p, 208.)
When a solution of nitrobenzene in methanol is boiled with sodium hydroxide,
the nitrobenzene is reduced to azoxybenzene by the methanol, which is itself
oxidised to formic acid.
4C 8 H 6 NO, + 3CH,OH + 3NaOH = 2C.H5NO:NCeH5 + 3HCOONa + 6H8O
The azoxybenzene in turn, when heated with iron filings, readily undergoes
C,H 6 NO:NC,H 6 + Fe = C 6 H 6 NrNC 6 H 4 + FeO
further reduction to azobenzene.
AZOXYBENZENE. Required: Sodium hydroxide, 23 g.;
nitrobenzene, 15 ml.; methanol, 120 ml.
Add 23 g. of powdered (or " flake1') sodium hydroxide to a
solution of 15 ml. (18 g.) of nitrobenzene in 120 ml. of methanol
contained in a 250 ml. short-necked bolt-head flask. Fix a
reflux water-condenser to the flask and boil the solution on a
water-bath for 3 hours, shaking the product vigorously at inter-
vals to ensure thorough mixing. Then fit a bent delivery-tube to
the flask, and reverse the condenser for distillation, as in Fig. 59,
p. ioo, or Fig. 23(0), p. 45). Place the flask in the boiling water-
bath (since methanol will not readily distil when heated on a
water-bath) and distil off as much methanol as possible. Then
pour the residual product with stirring into about 250 ml. of cold
water: wash out the flask with water, and then acidify the mixture
with hydrochloric acid. The crude azoxybenzene separates as a
heavy oil, which when thoroughly stirred soon solidifies, particu-
larly if the mixture is cooled in ice-water.
Then filter off the solid azoxybenzene at the pump, wash it
thoroughly with water, and drain well. Recrystallise from a
minimum of methylated spirit, allowing the hot solution to cool
spontaneously (with occasional stirring) until crystallisation
starts, and then cool in ice-water. If crystallisation is delayed,
* 4 SeCd" the solution with a trace of the crude product: if on the
other hand the azoxybenzene separates at first as an emulsion, add
methylated spirit, drop by drop, with stirring until the solution is
clear, and then allow the cooling to proceed as before. The
PREPARATIONS 213
azoxybenzene is obtained as very pale yellow crystals, m.p. 36°.
Yield of recrystallised material, 11 g.
The fact that a mixed azoxy-compound, such as />-toluenerazoxy-
benzene, CH 3 C 6 H 4 NO:NC 6 H 5 , exists in two isomeric forms, disproves
the earlier symmetric formula (A) alloted to azoxybenzene, and
PR N TR N-4.O confirms the formula (B), in which
^6n61N\ ^6tl5iN~~>U i • • •
I \Q I! the oxygen is joinedj i_by a co-ordm-
J-
ate link to one
(A) C6H6N/ C 6 H 6 N (B) nitrogen atom.
AZOBENZENE. Required: Azoxybenzene, 8 g.; iron filings,
^Sg-
Place % g. of the pure powdered azoxybenzene and 25 g.
of iron filings (both reagents being quite dry) in a 75 ml. dis-
tilling-flask F and mix thoroughly by shaking. Cork the flask
and fit to the side-arm a boiling-tube B to act as receiver (Fig. 66):
cut or file a groove G in the boiling-tube cork
to allow escape of air. Now heat the mixture
directly with the Bunsen flame, waving the
latter around the base of the flask to ensure
uniform heating: heat gently at first and later
more strongly. The red liquid azobenzene
distils over smoothly and eventually solidifies
in the receiver. When no more distillate passes X<~'XFIG. 66.
over, detach the boiling-tube, and then, in
order to eliminate basic impurities which are formed as by-
products in the reaction, add 20-30 ml. of dilute hydrochloric
acid (i vol. of concentrated acid : 2 vols. of water) which have
been heated to about 70°: cork the tube securely and shake the
mixture, so that impurities in the molten drops of azobenzene
are thoroughly extracted by the acid, which usually becomes dark
in colour. Now cool in water until the globules of azobenzene
solidify, and then filter at the pump. Break up the azobenzene
with a spatula on the filter, wash thoroughly with water, and
drain. Recrystallise from a minimum of boiling methylated spirit,
filtering the hot solution through a small fluted filter-paper. The
azobenzene separates as reddish-orange crystals, m.p. 67-68°.
Yield, 4 g. A second recrystallisation from methylated spirit
may be necessary to obtain a satisfactory melting-point.
In order to save the cost of the distilling-flask (which after the above
treatment is useless for further work), the mixture may be distilled from a
small retort made by blowing a suitable bulb on the end of a rather thick-
walled tube of about 8-10 mm. internal diameter: the tube is then bent
through almost 90° a few cm. above the bulb, cut to a suitable length, and the
open end fitted into the boiling-tube as before.
214 PRACTICAL ORGANIC CHEMISTRY
Methyl-orange (Sodium salt).
NaO3SC6H4N : NC6H4N(CH3)2.
When hydrochloric acid is cautiously added to an aqueous solution con-
taining both sodium nitrite and the sodium salt of sulphanilic acid,
NaO3SC6H4NH2, the amino group of the latter undergoes normal diazotisation,
giving the diazonium chloride (A). The latter, however, ionises in solution,
giving sodium and chloride ions and the internal salt (B), which possesses two
opposite charges and is therefore neutral: this internal salt is stable under
+ - - +
(A) NaO 3 SC 6 H 4 N 2 Cl -> Na + Cl + O 8 SC 6 H 4 N 2 (B)
these conditions, and being only moderately soluble in water, will be largely
precipitated unless the solution is very dilute. If now dimethylaniline hydro-
chloride is added to the solution, coupling will occur between the internal salt
and the tertiary amine, with the formation of methyl-orange:

On the addition of sodium hydroxide, the sparingly soluble sodium salt of


methyl-orange, NaO 3 SC 6 H 4 NiNC 6 H 4 N(CHs) 2 , will crystallise out.
It is important in this preparation to avoid an excess of nitrous acid before
coupling occurs, otherwise the excess of nitrous acid will react directly with the
dimethylaniline, and the deep green />-nitrosodimethylaniline so formed will
contaminate the methyl -orange.
Required: Anhydrous sodium carbonate, 2 g.; sulphanilic
acid, 7 g.; sodium nitrite, 2-2 g.; hydrochloric acid, 12 ml.;
dimethylaniline, 4 ml.
Dissolve 2 g. of anhydrous sodium carbonate in 50 ml. of
water contained in a 400 ml. beaker and add 7 g. of finely
powdered crystalline sulphanilic acid (2H 2 O), warming the mix-
ture gently in order to obtain a clear solution. Add a solution of
2-2 g. of sodium nitrite in io ml. of water and then cool the
mixture in ice- water until the temperature has fallen to 5°. Now
add very slowly (drop by drop) with continual stirring a solution
of 8 ml. of concentrated hydrochloric acid in 15 ml. of water: do
not allow the temperature to rise above 10°. When all the acid
has been added, allow the solution to stand in ice- water for 15
minutes to ensure complete diazotisation: during this period
fine crystals of the internal salt separate from the pink solution.
Dissolve 4 ml. of dimethylaniline in a mixture of 4 ml. of con-
centrated hydrochloric acid and io ml. of water, cool the solution
in ice-water, and add it slowly to the cold well-stirred diazo
solution: a pale red coloration is developed. Allow the mixture
to stand for 5 minutes and then add slowly with stirring aqueous
PREPARATIONS 215
10 % NaOH solution until the mixture attains a uniform orange
colour (about 50 ml. are required).
The sodium salt of methyl-orange separates as very fine particles,
and filtration, if attempted directly, may be very slow. Therefore
warm the mixture to 50-55°, stirring it meanwhile with a ther-
mometer: when nearly all the methyl-orange has dissolved, add
about 10 g. of finely powdered sodium chloride, and continue
warming for a few minutes until the chloride itself has dissolved.
Now allow the mixture to cool spontaneously for 10-15 minutes,
and then cool in ice-water. Filter off the methyl-orange at the
pump: filtration is now rapid, particularly if only gentle suction
is employed, so that the particles of the methyl-orange are not
dragged into the pores of the filter-paper. Drain thoroughly, and
then recrystallise the methyl-orange from about ioo ml. of boiling
water: filter the hot solution (if necessary) through a fluted filter-
paper in a heated funnel, or a Buchner funnel which has been
preheated by the filtration of some boiling water. The deep
reddish-orange crystals of methyl-orange separate rapidly as the
solution cools. Yield, 9 g.
The use of methyl-orange as an indicator is based on the fact that the sodium
salt in aqueous solution furnishes a yellow anion, which when treated with acids
(except weak acids such as H 2 CO 3 and H 2 SO 3 ) apparently gives rise to a red

N = N^ >N(CH 3 ) 2 (yellow)

alkalis || acids (e.g. HCl)


/=\ +
NH-N=(Q \=N(CH 3 ) 2 (red) + Cl

quinonoid cation, the change being reversed by alkalis. It is possible, however,


that there are additional factors governing these colour changes.

Benzidine or 4,4'-Diamino-biphenyL*
TV C* Wn4**"'6
H 2^*v-»6- C* W riL TMU
4*i^ri>2*
When hydrazobenzene, or sym-diphenylhydrazine, is warmed with acids, it
undergoes an intramolecular rearrangement, with the formation of benzidine,

C 6 H 6 -NH-NH-C 8 H 5 —*• H 2 N

or 4,4'-diamino-biphenyl. This reaction is of wide application and is known as


the Benzidine Transformation.
Required: Hydrazobenzene, 10 g.; zinc dust, 10 g.
HYDRAZOBENZENE. The above preparation of benzidine
* See footnote, p. 216.
216 PRACTICAL ORGANIC CHEMISTRY
should be carried out with pure hydrazobenzene. This com-
pound, however, when kept in store undergoes atmospheric
oxidation to azobenzene (p. 212), and such samples are therefore
usually orange-red in colour due to contamination with azo-
benzene If the hydrazobenzene is coloured in this way, it should
be purified by the following process, which reduces any
azobenzene back to hydrazobenzene.
Add io g. of the crude hydrazobenzene to 80 ml. of ethanol
contained in a flask fitted with a reflux water-condenser. Heat the
mixture on a water-bath until the ethanol boils, and then add
io g. of zinc dust and 30 ml. of 30% aqueous sodium hydroxide
solution. Remove the flask from the water-bath and shake the
contents vigorously from time to time. After about io minutes,
replace the flask on the water-bath and boil the contents for 3-5
minutes. Filter the mixture at the pump, transfer the filtrate to a
beaker and cool in ice-water with stirring. The hydrazobenzene
separates as colourless crystals, which are filtered off at the pump
and drained. A portion when dried in a desiccator has m.p.
124°.
BENZIDINE. Add 5 g. of the thoroughly drained (and
almost dry) hydrazobenzene to a mixture of 15 ml. of concentrated
hydrochloric acid and ioo ml. of distilled water contained in
a 250 ml. conical flask. Warm the mixture to 25-30°, and then
securely cork the flask and shake the contents vigorously.
Occasionally withdraw the cork, and re-warm the mixture before
shaking again. After about 15 minutes, heat the mixture care-
fully to 50° for about 5 minutes. If the original hydrazobenzene
were pure, a clear solution should now be obtained. If any
undissolved material remains, however, filter the solution, and
precipitate the benzidine by the addition of aqueous sodium
hydroxide solution to the cooled filtrate. Filter off the precipi-
tated benzidine, and recrystallise from boiling water (in which it
is only moderately soluble), adding some animal charcoal to the
boiling solution if it is coloured.* The benzidine separates from
the cooled filtrate as a monohydrate, which when placed in a
vacuum desiccator readily gives the anhydrous benzidine as
colourless crystals, m.p. 127°, A second recrystallisation from
water is however sometimes necessary. Yield, 2-5 g. Alter-
natively, the crude precipitated benzidine can be recrystallised
from ethanol, or it may be dried and recrystallised from benzene.
* Care. Benzidine is carcinogenic, and strict care should be taken not to
absorb it either by inhalation or bv contact \\ith the skin.
PREPARATIONS 217
TV-Phenylanthranilic Acid, C 6 H 5 -NH-C n H 1 -COOH.
(The Ullmann Condensation.)
A halogen atom directly attached to a benzene ring is usually unreactive,
unless it is activated by the nature and position of certain other substituent
groups. It has been shown by Ullmann, however, that halogen atoms normally
of low reactivity will condense with aromatic amines in the presence of an alkali
carbonate (to absorb the hydrogen halide formed) and a trace of copper powder
or oxide to act as a catalyst. This reaction, known as the Ullmann Condensation,
is frequently used to prepare substituted dipheny !amines: it is exemplified

O
COOH

in the following condensation of o-chlorobenzoic acid \vith aniline to give


N-phenylanthranilic acid or o-carboxydiphenylamine.
Required: Aniline, 30 ml.; o-chlorobenzoic acid, 8 g.; potas-
sium carbonate, 8 g.; powdered copper oxide, 0-4 g.
Prepare a mixture of 30 ml. of aniline, 8 g. of o-chloro-
benzoic acid, 8 g. of anhydrous potassium carbonate and 0-4 g.
of copper oxide in a 500 ml. round-bottomed flask fitted with
an air-condenser, and then boil the mixture under reflux for
1-5 hours: the mixture tends to foam during the earlier part of
the heating owing to the evolution of carbon dioxide, and hence
the large flask is used. When the heating has been completed, fit
the flask with a steam-distillation head, and steam-distil the crude
product until all the excess of aniline has been removed. The
residual solution now contains the potassium .Y-phenylanthrani-
late: add ca. 2 g. of animal charcoal to this solution, boil for
about 5 minutes, and filter hot. Add dilute hydrochloric acid
(1:1 by volume) to the filtrate until no further precipitation
occurs, and then cool in ice-water with stirring. Filter otl the
A -phenylanthranilic acid at the pump, wash with water, drain
and dry. Yield, 9-9*5 g. The acid may be recrystallised from
aqueous ethanol, or methylated spirit, with addition of charcoal
if necessary, and is obtained as colourless crystals, m.p. 185-186°.
For the cyclisation of A 7 -phenylanthranilic acid to acridone, see p. 303 .

Methylation can be carried out by the following methods:


(i) Williamson s Method, more particularly for hydroxy- and thiol- (mercapto)
compounds. The substance is treated either directly with sodium or (more
usually) with a solution of sodium methoxide in methanol, to give the sodium
derivative. The latter is then boiled with methyl iodide.
ROXa ICH 3 — ROCH 3 XaI
2i8 PRACTICAL ORGANIC CHEMISTRY
Note that this is only a particular case of Williamson's general method for the
preparation of ethers.
(2) Purdie's Method, also chiefly for hydroxy-compounds. The substance
is mixed with a small excess of dry silver oxide, and then shaken (or, if neces-
sary, heated) with methyl iodide, a smooth methylation usually occurring.
2 ROH + Ag4O + 2 CH,I = 2ROCH, + 2AgI + H1O

This method is used more particularly for hydroxy-compounds which also


contain other groups (such as Cl atoms, etc.) which might be affected by the
sodium hydroxide used in the following method.
(3) Dimethyl Sulphate Method, for hydroxy-compounds and for primary
and secondary amines, acid amides, etc. The substance is dissolved or sus-
pended in water, a small excess (above the theoretical) of sodium hydroxide
added and then the theoretical quantity of dimethyl sulphate, the mixture
being finally shaken without external warming. Methylation is usually
rapid, the dimethyl sulphate being converted to methyl hydrogen sulphate
ROH + (CH 3 )^SO 4 + NaOH = ROCH8 + CH3NaSO4 + H2O
RNH 2 + (CHa) 2 SO 4 + NaOH = RNHCH 8 4- CH3NaSO4 + H,O
which dissolves in the alkali present. The general conditions are thus very
similar to those used for the Schotten-Baumann reaction (p. 243) by which the
same classes of compound (hydroxy-derivatives, primary and secondary amines)
can be benzoylated, etc.
For the preparation of tertiary amines, the conditions must not be too vigorous,
otherwise the tertiary amine may react further to form the quaternary methyl
methosulphate.
For experimental details, see p. 220.
Dimethyl sulphate is poisonous, both when the hot vapour is inhaled and even
ichen the cold liquid is spilt on the hands, and considerable care should be exercised
in its use (cf. pp. 215, 218, 526).
(4) Diazornethane Method. Diazomethane readily methylates phenolic
hydroxy-compounds, primary and secondary amines, and carboxylic acids,
ROH + N1CH, = ROCH8 + N1
nitrogen being liberated. Since diazomethane is a gas, it is usually employed
in ethereal solution. One advantage of this method of methylation is that it
takes place in an almost neutral solution, i.e., the addition of alkalis or acids is
unnecessary. Diazomethane is both poisonous and (in the gaseous state) explosive,
and requires therefore careful manipulation.
(5) The Formaldehyde-Formic Acid Method. This method applies to primary
and secondary amin.es, which when boiled with a formalin-formic acid mixture
undergo complete methylation to the corresponding tertiary amine. This
method has the advantage over the dimethyl sulphate method in that quaternary
salts clearly cannot be formed.
The mechanism of this methylation is probably that the primary amine
RNH 1 -> RN:CH a -* RNHCH, -> RN(-CH,OH)CH, -» RN(CH1),
(I) (U) (HA) (III)
condenses with the formaldehyde to give a Schiff's base (I) [or an analogous
PREPARATIONS 219
compound RNH(1CH8OH)], which is then reduced to the secondary amine (II)
by the formic acid, which is itself oxidised to carbon dioxide. The secondary
amine then undergoes a similar conversion through the intermediate (I IA) to
the tertiary amine (III). For experimental details, see p. 226.
Methods (2) and (3) have been extensively used in the investigation of the
structure of sugars.

Anisole (Methyl Phenyl Ether). C6H5OCH3. (Method i.)


Required: Sodium, 3-8 g.; methanol, 75 ml.; phenol, ^15 g.;
methyl iodide, n ml.
Weigh out 3-8 g. of metallic sodium, cut it into small pieces,
and add it to 75 ml. of good-quality (preferably absolute)
methanol contained in a 250 ml. bolt-head flask: at once attach the
flask to an efficient reflux water-condenser. Considerable heat
is evolved by the dissolution of the sodium, and the alcohol boils
vigorously under reflux: no attempt should be made to cool the
alcohol (unless the condenser tends to "choke"), otherwise a
considerable time will elapse before the last traces of the sodium
dissolve. Then cool the clear solution of sodium methoxide in
ice-water, and add 15 g. of phenol,* which will rapidly dissolve
to give sodium phenoxide (or phenate) when the mixture is gently
shaken. Now add n ml. (25 g., i-i mols.) of methyl iodide
and some fragments of unglazed porcelain, re-attach the flask to
the reflux condenser, and boil the solution gently on a water-bath
for one hour. Then remove the flask from the water-bath, and
rearrange the condenser for direct distillation, connecting it
through a "knee-tube" to the flask (as in Fig. 59, p. ioo, or Fig.
23(0), p. 45). Replace the latter on the water-bath, and distil off
the excess of methanol as completely as possible. Pour the residual
liquid in the flask into ioo ml. of cold water contained in a separa-
ting-funnel, and wash out the flask with another 50 ml. of water,
adding these washings also to the liquid in the funnel. Then
extract the anisole by shaking with about 40-50 ml. of ether. Run
off the lower aqueous layer, and shake the ethereal solution with
an equal volume of 10% aqueous sodium hydroxide solution: this
removes unchanged phenol, and also any traces of free iodine
present, leaving the ethereal solution quite colourless. Run off the
sodium hydroxide solution as completely as possible, and shake the
ethereal solution with an equal volume of water to remove the last
traces of the sodium hydroxide. Separate the ethereal solution,
* The phenol should be weighed out carefully on a piece of glazed paper on the
balance pan. If spilt crystals of phenol are allowed to remain on the balance
pans, the latter may become corroded. If phenol is allowed to come in contact
with the hands, it should be washed off without delay.
220 PRACTICAL ORGANIC CHEMISTRY
dry it with calcium chloride, and then distil off the ether from
the filtered solution in a 50 ml. distilling-flask, using a similar
apparatus and observing the same precautions as in the prepara-
tion of aniline (see Fig. 64, p. 163, or Fig. 23(E), p. 45). When
all the ether has been distilled off, replace the water-condenser
by an air-condenser, and distil the residual anisole slowly over a
gauze. Collect the fraction distilling at 152°-!56°. Yield, 9 g.
Anisole is a colourless and almost odourless liquid, having b.p.
154°, and d, 0-99. Like the aliphatic ethers, it is chemically
inert, although of course the phenyl group shows the normal
aromatic reactions.
Phenetole. (Ethyl Phenyl Ether.) C 6 H 5 OC 2 H 5 . (Method I3
p. 217.)
In view of the high cost of methyl iodide in the above preparation of anisole,
and the fact that, unless absolute methanol is used, the ready hydrolysis of the
methyl iodide may cause a low yield of the ether, the preparation of anisole
may be advantageously replaced by that of phenetole. The reaction is not of
course a methylation, but is nevertheless of the same type as that used in the
preparation of anisole.
Required: Sodium, 3-8 g.; ethyl bromide, 13-2 ml. (19*1 g.); phenol>
15 g:
Dissolve 3-8 g. of sodium in 75 ml. of rectified spirit, using other-
wise the same conditions as in the preparation of anisole. Then add
15 g. of phenol, and to the clear solution add 13-2 ml. (19-1 g., ri
mols.) of ethyl bromide. Continue precisely as in the preparation of
anisole, shaking the ethereal extract with sodium hydroxide solution as
before in order to eliminate any unchanged phenol. Finally collect the
fraction boiling at 168-172°. Yield, 14 g.
Phenetole is a colourless liquid, having b.p. 171°, and d, 0-98.
Methyl 2-Naphthyl Ether. (Nerolin.) C10H7OCH3.
(Method 3, p. 218.)
Experiments involving the use of dimethyl sulphate should be carried
out by students only under immediate supervision. Not only is the
vapour of dimethyl sulphate highly poisonous^ but the cold liquid itself is
absorbed easily through the skin, with toxic results: individual sus-
ceptibility to dimethyl sulphate poisoning varies and may be very high.
If the sulphate is splashed on to the hands, wash immediately with
plenty of concentrated ammonia solution in order to hydrolyse the methyl
sulphate before it can be absorbed through the skin (see p. 528).
Required: 2-Naphthol, 10 g.; dimethyl sulphate, 6-9 ml. (9-2 g.).
Dissolve 10 g. of pure 2-naphthol in 30 ml. of 10% sodium
hydroxide solution (IT mols.) contained in a stout-walled wide-
necked bottle of about 200 ml. capacity, and for which a well-
PREPARATIONS 221
fitting rubber stopper is available. Dilute the solution with 30
ml. of water in order to moderate the subsequent reaction, and
then run in from a burette 6*9 ml. (9*2 g., 1*05 mols.) of
dimethyl sulphate. Cork the bottle securely and shake the
contents vigorously. As the reaction proceeds, the mixture
becomes warm and the methyl naphthyl ether rapidly separates
as a greyish-white powder: finally after about 20 minutes' shaking
the reaction is complete and the mixture has again become almost
cold. Filter the methyl naphthyl ether at the pump, wash with
dilute (io%) sodium hydroxide to remove any traces of un-
changed naphthol or methyl sulphate, and then wash thoroughly
with water and drain.
Recrystallise from methylated spirit, from which the methyl
2-naphthyl ether separates readily as colourless crystals, m.p.
72°: yield, Q g .
Nerolin, which has a faint but persistent odour, is used tech-
nically for scenting soaps, etc.
i-Naphthol, similarly methylated, gives the liquid methyl i-naphthyl ether,
b.p. 263°. Phenol gives anisole, the preparation of which by Method i has,
however, already been described.
Toluene-/?-sulphon-dimethylamide.*
CH3C6H4SO2N(CHg)2. (Method 3, p. 218.)
Toluene-/>-sulphonamide can be similarly converted into the dimethyl-
amide, but the methylation now occurs in two definite stages. First the
sulphonamide dissolves in the sodium hydroxide to form the mono-sodium salt
(see p. 252), which then reacts with the dimethyl sulphate to give the mono-
CH 3 C 6 H 4 SO 2 NHNa + (CH3)2SO4 = CH 3 C 6 H 4 SO 2 NH(CH 3 ) + NaCH 3 SO 4
methylamide: the latter, being still acidic, remains dissolved in the alkaline
solution as the sodium salt, which then reacts with a second equivalent of
CH 8 C 6 H 4 SO 2 NNa(CH 8 ) + (CH3)2SO4 = CH 3 C 6 H 4 SO 2 N(CH 3 ), H- NaCH 8 SO 4
dimethyl sulphate to give the dimethylamide. The dimethylamide is neutral
and therefore separates from solution.
Required: Toluene-p-sulphonamide, io g.; dimethyl sulphate,
127 ml. (17 g.).
Dissolve io g. of powdered toluene-p-sulphonamide in 6o ml.
of io % aqueous sodium hydroxide (2-5 mols.) diluted with
50 ml. of water to moderate the reaction. Then, using the same
precautions as in the previous preparation, add 12-7 ml. (17 g.,
2-3 mols.) of dimethyl sulphate and shake the mixture vigorously.
The crystalline dimethylamide rapidly separates from the warm
* Alternative name: A T ,A'-dimethyltoluene-/>-su1phonamide.
222 PRACTICAL ORGANIC CHEMISTRY
solution. After 15-20 minutes' shaking, cool the mixture in ice-
water, and filter off the dimethylamide. Wash with sodium
hydroxide solution, then with water and drain. The product
thus prepared is (when dry) almost pure, but can be readily re-
crystallised from a mixture of equal volumes of water and glacial
acetic acid: filter the recrystallised material at the pump, wash
with water, drain and dry. Colourless crystals, m.p. 79°: yield,
8g.
The toluene-p-sulphon-dimethylamide can be readily hydrolysed
by boiling under reflux with 70% sulphuric acid (see p. 107). If the
CH 3 C 6 H 4 S0 2 N(CH 3 ) 2 + H2O + H 9 SO 4 ->- CH 3 C 6 H 4 SO 2 OH +
(CH 3 J 2 NH 1 H 2 SO 4
clear solution so obtained is placed in a distilling-flask and made alka-
line, the liberated dimethylamine may be driven over by heating,
and then absorbed in hydrochloric acid. Evaporation of the hydro-
chloric acid solution gives the deliquescent crystalline dimethylamine
hydrochloride, (CH 3 ) 2 NH,HC1.

tf-Methylanthranilic Acid. CH3 NH C6H4 COOH.


(Method 3, p. 218.)
This preparation illustrates the use of dimethyl sulphate to convert a primary
amino group into the secondary monomethylamino group, without the methy-
lation proceeding to the tertiary dimethylamino stage. The methylation of
anthranilic acid is arrested at the monomethylamino stage by using i-i mole-
cular equivalents of sodium hydroxide and of dimethyl sulphate. The reactions
can be considered as:
NH 2 -C 6 H 4 -COOH + NaOH -* NH 2 -C 8 H 4 -COONa + H2O
NH 2 -C 6 H 4 -COONa -f (CH 3 ) 2 SO 4 -> CH 3 -NH-C 6 H 4 -COOH + NaCH 3 SO 4
The isolation of the A T -methylanthranilic acid is greatly facilitated by the fact
that in cold water it is appreciably less soluble than anthranilic acid, and very
much less soluble than ATAT-dimethylanthranilic acid.
Required: Anthranilic acid, 2 g.; dimethyl sulphate, 1-6 ml.
(2 g-)-
A fresh sample of dimethyl sulphate should be employed: an old
sample, or one that has been frequently exposed to the air, should be
shaken with water, separated, dried over sodium sulphate, and distilled
(b.p. 188°).
Dissolve 2 g. of anthranilic acid in 12-8 ml. of 5% aqueous
sodium hydroxide, or in 16 ml. of TV-NaOH solution in a 50 ml.
conical flask. (It is essential that the concentration of the
hydroxide solution is accurately known.) Add i -6 ml. of dimethyl
sulphate, and shake the securely-stoppered flask vigorously.
PREPARATIONS 223
The N-methylanthranilic acid rapidly separates. Cool the mix-
ture in ice-water, filter off the acid at the pump, wash thoroughly
with water and drain. The crude acid if now dried weighs
1-5 g. and has m.p. 166-170°.
To save time, the well-drained acid may be recrystallised twice
from ethanol, and the pure acid, m.p. 176-177°, thus obtained.
This recrystallised acid is "pure" in the normally accepted sense of
the word, namely it has a sharp m.p. and gives on analysis excellent
values for carbon, hydrogen and nitrogen. If however it is subjected
to one-dimensional paper chromatography (p. 53), the presence of
traces of unchanged anthranilic acid can be detected, and repeated
recrystallisation is necessary to remove these traces.
i-Phenyl-ethylamine. CH3-CH(C6H5)NH2.
(The Leuckart Reaction.)
Aldehydes and ketones may be converted into the corresponding primary
amines by reduction of their oximes or hydrazones (p. 93). A method of
more limited application, known as the Leuckart Reaction, consists of heating
the carbonyl compound with ammonium formate, whereby the formyl-amino
derivative is formed, and can be readily hydrolysed by acids to the amine.
Thus acetophenone gives the i-phenylethylformamide, which without isolation
can be hydrolysed to i-phenylethylamine.
CH3-CO + 2HCOONH4 -> CH3-CH-NH-CHO + CO8 + NH 8 + 2H8O
C8H5 C6H5
CH8-CH-NH CHO + H2O -* CH8-CH-NH, + HCOOH
C8H8 C6H5
The reaction proceeds most readily with alkylaryl, dialkyl, and cyclic ketones,
but the crude product may contain some secondary or tertiary amine.
Required: Acetophenone, 30 g.; ammonium formate, 50 g.;
benzene, 30 ml.; hydrochloric acid, 30 ml.; ether, ioo ml.,
sodium hydroxide.
Fit a ioo ml. Claisen flask with a thermometer reaching almost
to the bottom of the flask, and a water-condenser for distillation.
Place in the flask 30 g. of acetophenone and 50 g. of dry ammo-
nium formate (with some unglazed porcelain), and heat the mix-
ture gently over a small flame. The mixture readily forms two
layers and distillation begins: at 150-155° the reaction starts with
moderate effervescence. Continue heating until the temperature
of the mixture reaches 185°, and then allow to cool. The dis-
tillate has meanwhile separated into two layers, the upper layer
being mainly unchanged acetophenone. Separate this upper
layer, return it to the flask, and continue heating the mixture at
180-185° for 30-40 minutes.
Cool the reaction mixture, transfer it to a separating-funnel,
224 PRACTICAL ORGANIC CHEMISTRY
and extract it with 40 ml. of water to remove ammonium formate
and formamide. Run the lower layer of i-phenylethylformamide
back into the original flask, and extract the upper aqueous layer
with 30 ml. of benzene. Discard the aqueous layer, and run the
benzene extract also into the flask. Now add 30 ml. of concen-
trated hydrochloric acid and some porcelain, and distil off the
benzene: then boil the residual liquid gently under reflux for
30 minutes. Cool the liquid, and extract it with 25 ml. of benzene
to remove traces of acetophenone. Chill the aqueous layer
thoroughly and then liberate the amine by slowly adding with
stirring a solution of 25 g. of sodium hydroxide in 50 ml. of water.
Extract the mixture twice with ether (50 ml. each time) and dry
the united ethereal extracts over solid sodium hydroxide. Then
distil off the ether from the filtered extract, and finally the i -phenyl-
ethylamine, b.p. 185-188°. Yield, 12-13 g. The small higher-
boiling residue is di-i-phenylethylamine, (CH 3 CH-C 6 H 5 ) 2 NH.
2-Dimethylamino-jf-octane from /i-Octan-2-ol.
This complete preparation entails four consecutive intermediate preparations
each illustrating a standard reaction in organic chemistry.
ti-Octan-2-ol (A), sometimes called sec.octyl alcohol, can be obtained, at a
low price and of high purity, from technical sources. As a secondary alcohol,
it can be readily oxidised by potassium dichromate-sulphuric acid to n-hexyl
(A) CH3(CH2VCH(OH)-CH3
I
(B) CH8(CH2VCOCH,
I
(C) CH3(CH8VC-CH,
I NOH
(D) CH8(CH1VC1H-CH,
J NH 8
(E) CH8(CH2VCH-CH8
N(CH1),
methyl ketone (B). This ketone gives with hydroxylamine an oxime (C),
which is purified by distillation under reduced pressure. The oxime is reduced
by sodium and ethanol to 2-?mino-n-octane (D). This primary amine, when
boiled with a formaldehyde-formic acid mixture (p. 218), undergoes methylation
to the tertiary amine 2-dirnethylamino-n-octane (E).
Required: n-Octan-2-ol (redistilled), 61 ml. (50 g.); sodium
dichromate dihydrate, 37-5 g.; hydroxylamine sulphate, 80 g. (or
the hydrochloride, 68-5 g.); hydrated sodium acetate, 25 g.;
sodium, 38 g.; 40% formalin solution, 50 ml.; formic acid, 80 ml.;
ethanol, 250 ml.
PREPARATIONS 225
(B) w-HEXYL METHYL KETONE. CH 3 (CH 2 ) 6 -CO-CH 3 .
Redistil technical n-octan-2-ol, and collect the fraction of
b.p. 178-179°. Fit a three-necked round-bottomed flask of ca.
500 ml. capacity with a stirrer, dropping-funnel and reflux
water-condenser (as in Fig. 23(0), p. 46). Place 250 ml. of water
in the flask, cautiously add with stirring 27-5 ml. (50 g.) of con-
centrated sulphuric acid, and then add 37*5 g. of pulverised
sodium dichromate dihydrate. To this stirred solution add 61 ml.
(50 g.) of n-octan-2-ol from the dropping-funnel during 45
minutes. Then heat the reaction-mixture under reflux on a
boiling water-bath for i hour. Transfer the solution to a steam-
distillation apparatus (or fit a steam-distillation head to the
original flask) and steam-distil the mixture until no more ketone
passes over. Separate the insoluble ketone from the aqueous
distillate, and dry it over calcium chloride. After filtration, distil
the w-hexyl methyl ketone, b.p. 172-173°. Yield, 40 g.
(C) n-HEXYL METHYL KETOXIME.
CH3(CH2)5C(:NOH)-CH3.
Place 80 g. of hydroxylamine sulphate (or 68-5 g. of the hydro-
chloride), 25 g. of hydrated sodium acetate, and ioo ml. of
water in a 500 ml. flask fitted with a stirrer and a reflux water-
condenser, and heat the stirred solution to 55-60°. Run in
35 g. (42 ml.) of n-hexyl methyl ketone, and continue the heating
and vigorous stirring for i j hours. (The mixture can conveni-
ently be set aside overnight after this stage.) Extract the oily
oxime from the cold mixture twice with ether. Wash the united
ethereal extract once with a small quantity of water, and dry it
with sodium sulphate. Then distil off the ether from the filtered
extract, preferably using a distillation flask of type shown in
Fig. 41 (p. 65) and of ca. 50 ml. capacity, the extract being run
in as fast as the ether distils, and then fractionally distil the
oxime at water-pump pressure. Collect the liquid ketoxime, b.p.
iio-in°/i3 mm. Yield, 30-32 g.
(D) 2-AMINO-n-OCTANE. CH 3 (CH 2 ) 6 CH(-NH 2 )-CH 3 .
For this reduction use preferably a i litre round-bottomed flask
having 3 necks (Fig. 23(0), p. 46), the two necks at the flanks
being straight (to avoid the obstruction, during the addition of
sodium, which a curved neck might cause). Fit the central neck
with a stirrer, one of the side necks with a reflux water-condenser,
and the other with a glass or rubber stopper.
Place 25 g. (29 ml.) of the oxime and ioo ml. of ethanol in the
flask, and heat the stirred solution under reflux on a boiling
226 PRACTICAL ORGANIC CHEMISTRY
water-bath. Meanwhile cut up 38 g. of sodium into small pieces
of convenient size for inserting through the third neck of the
flask, and store them temporarily in a wide-necked bottle closed
by a cork. Add the pieces of sodium in turn to the stirred boiling
solution, removing each piece from the bottle by means of for-
ceps or tongs: when the reaction appears to be subsiding add
more ethanol (150-200 ml.) in small portions to maintain a
vigorous reaction, and to complete the dissolution of the sodium
(total time, i|-2 hours).
Discontinue the heating, and add 125 ml. of water cautiously
from a dropping-funnel to the stirred hot solution. Then either
pour the solution into a flask fitted for steam-distillation, or
adapt the 3-necked flask by replacing the stirrer by a steam-head
to which the reversed condenser can be fitted, the other two
necks being closed unless the design of the steam-head necessi-
tates the steam being led in through one of these necks. Collect
about 750 ml. of distillate in a flask containing ca. 20 ml. of con-
centrated hydrochloric acid. Evaporate the acidic mixture to
30-40 ml. on a water-bath (to save time, start evaporating the
first 50-100 ml. of distillate as soon as it is collected, and add the
remainder in portions whilst the distillation is proceeding).
Chill the concentrated solution of the amine hydrochloride in
ice-water, and then cautiously with stirring add an excess of 20 %
aqueous sodium hydroxide solution to liberate the amine. Pour
the mixture into a separating-funnel, and rinse out the flask or
basin with ether into the funnel. Extract the mixture twice with
ether (2 X 25 ml.). Dry the united ether extracts over "flake" or
powdered sodium hydroxide, preferably overnight. Distil the
dry filtered extract from an apparatus similar to that used for the
oxime: when the ether has been removed, distil the amine slowly
under water-pump pressure, using a capillary tube having a soda-
lime guard-tube to ensure that only dry air free from carbon dioxide
passes through the liquid. Collect the amine, b.p. 59-61°/12
mm.: at atmospheric pressure it has b.p. 163-164°. Yield, 18 g.
To prepare a sample of the hydrochloride, add 0-5 ml. of the base to 10 ml. of
dilute hydrochloric acid in an evaporating basin and evaporate to dryness, pre-
ferably in a vacuum desiccator. Recrystallise the dry residue from petroleum
(b.p. 60-80°). The hydrochloride separates as white crystals, m.p. 90°.

(E) 2-DIMETHYLAMINO-n-OCTANE.
CH 3 -(CHO 5 -CHf-N(CH 8 )J-CH 1 .
Dissolve 12 g. of the amine in 50 ml. of fresh 40% formalin in
a flask fitted with a reflux water-condenser. Cool the mixture,
PREPARATIONS 227
add slowly 70 ml. of formic acid down the condenser, and then
boil the mixture under reflux for i\ hours, during which time
carbon dioxide is steadily evolved.
Cool the solution thoroughly in ice-water, and then make it
alkaline by the cautious addition (with stirring or shaking) of a
solution of 80 g. of sodium hydroxide in ca. 150 ml. of water.
Now isolate the free tertiary amine by steam-distillation into
hydrochloric acid, etc., precisely as for the primary amine in
Stage (D), but preferably using a smaller flask for the final dis-
tillation. Collect the 2-dimethylamino-n-octane, b.p. 76-78°/15
mm. Yield, 13-14 g. At atmospheric pressure the amine has
b.p. 187-188°.
The hydrochloride of the amine may be prepared precisely as that of the
primary amine. For recrystallisation, boil a suspension of the powdered salt in
petroleum (b.p. 60-80°), and then add acetone slowly in small drops until the
boiling suspension just becomes clear: allow the stirred solution to cool until
crystallisation starts, and then chill in ice-water before collecting the colourless
plates of the hydrochloride, which after drying in a vacuum desiccator have
m.p. 132-134°.
Both the primary amine (D) and the tertiary amine (E) are
reasonably strong bases, and will absorb carbon dioxide if
exposed to the air. They should therefore be stored in ground-
glass stoppered bottles or in sealed tubes.
Caprolactam. The Beckmann Rearrangement.
The oximes of ketones when treated with various acidic reagents undergo the
Beckmann Rearrangement, whereby, e.g., the -OH group in the oxime (I) can
be regarded as undergoing a trans exchange with the group R1, followed by back
migration of the H atom, to give the substituted acid amide (II). This process
H2 H8
C C
1 2 2
R R O R / \ / \
\ / \ / H1C CH, HtC CH2
C -> C I I - I I
Il I H8C CH8 H8C CH 2
N-OH NHR 1 \ / I I
C O:C NH
N-OH
(I) (II) (III) (IV)
when applied to the oxime of an alicyclic ketone will therefore give a cyclic
lactam with ring enlargement: cyclohexanone-oxime (III) will thus give the
lactam (IV) of e-amino-caproic acid, or caprolactam, which systematically is a
cyclic acid amide. In this example, 85 % sulphuric acid is used as the reagent.
228 PRACTICAL ORGANIC CHEMISTRY
Required: Cyclohexanone, 20 g.; hydroxylamine hydrochloride,
17 g.; anhydrous sodium carbonate, 13 g.; concentrated sul-
phuric acid, 50 ml.; 25% aqueous potassium hydroxide solution,
approx. 200 ml.; chloroform, 120 ml.
Cyclohexanone oxime. Add 20 g. (21 ml.) of cyclohexanone
to a solution of 17 g. of hydroxylamine hydrochloride in 40 ml.
of water, and cool the mixture in ice-water. Add a solution of
13 g. of anhydrous sodium carbonate in 40 ml. of water slowly
to the mixture, stirring the latter with a ioo° thermometer, and
maintaining the temperature of the mixture at 20-25° mean-
while. The oxime rapidly separates. Stir the complete mixture
at intervals, and after 10 minutes filter the oxime at the pump,
drain thoroughly and dry it in a (vacuum) desiccator. Yield of
crude oxime, 20 g. Recrystallise from petroleum (b.p. ioo-
120°) and dry over paraffin wax (p. 19). Yield of pure oxime,
16 g., m.p. 88°.
Beckmann Rearrangement. Prepare the 85 % sulphuric acid by
adding 50 ml. of the concentrated acid cautiously to 10 ml. of
water, stirring the mixture meanwhile, and then cool the diluted
acid in ice-water. Place 16 ml. of the cold acid in a 500 ml.
beaker, add 8 g. of the pure oxime, and warm the mixture
cautiously until effervescence begins, and then at once remove
the heat. A vigorous reaction occurs, and is soon complete.
Repeat this operation with another 8 g. of the oxime in a second
beaker: the reaction is too vigorous to be carried out with larger
quantities.
Unite the two reaction-mixtures and cool in ice-salt: add
40 g. of crushed ice to the mixture, and stir it mechanically
whilst slowly adding 25 % aqueous potassium hydroxide solution
(about 200 ml.) until the mixture is faintly alkaline to phenol-
phthalein: ensure that the temperature does not rise above 20°
during this operation. A considerable amount of potassium
sulphate crystallises from the mixture. Filter the latter at the
pump, and wash the residual sulphate on the filter with 30 ml.
of chloroform. Run the filtrate and washings into a separating-
funnel, run off the chloroform, and extract the aqueous layer
three times with chloroform, using 30 ml. on each occasion.
Dry the united chloroform extracts with sodium sulphate, filter,
and distil ofT the chloroform, finally distilling the residual capro-
lactam at water-pump pressure. It distils at 140-142°/i5 mm.,
and solidifies in the receiver. Yield, 10 g. from 16 g. of oxime.
The caprolactam, m.p. 68-70°, may be recrystallised from petrol-
eum (b.p. 60-80°) and obtained as colourless plates, m.p. 69-70°.
PREPARATIONS 229
Benzaldehyde Phenylhydrazone. C6H6CHzN-NHC6H6.
(Semi-micro Scale.)
Phenylhydrazine condenses readily with aldehydes and ketones to give
phenylhydrazones, which, being usually crystalline compounds of sharp

C 6 H 5 CHO -f H 2 NNHC 6 H 5 -> C 6 H 5 CHiNNHC 6 H 5 -f H 2 O


Benzaldehyde Phenylhydrazine Benzaldehyde
Phenylhydrazone
melting-point, can therefore be used to identify the aldehydes and ketones
from which they have been formed. For this purpose phenylhydrazones are
frequently more suitable than oximes (p. 93) since their greater molecular
weight causes a lower solubility in most solvents, and they can therefore often
be more easily isolated and recrystallised. The phenylhydrazones of the
lower aliphatic aldehydes and ketones, however, often have low melting-points,
and are thus not suitable for identification purposes: to overcome this
difficulty, substituted phenylhydrazines such as />-nitrophenylhydrazine,
(NO 2 C 6 H 4 NHNH 2 ), 2,4-dinitrophenylhydrazine (pp. 263, 346), and p-bromo-
phenylhydrazine are often used, since the corresponding substituted phenyl-
hydrazones usually crystallise well, and are of low solubility and high melting-
point.
Phenylhydrazine is usually dissolved in acetic acid for hydrazone formation:
if a salt of phenylhydrazine with an inorganic acid is used, it must be mixed
with an excess of sodium acetate (see preparation of osazones, p. 137).

Required: Acetic acid, 0-3 ml.; phenylhydrazine, 0*4 ml.;


benzaldehyde, 0-2 ml.
Dissolve 0-3 ml. of glacial acetic acid in 2 ml. of water in a 25
ml. conical flask, and add 0-4 ml. (0-44 g.) of phenylhydrazine.
Mix thoroughly to obtain a clear solution of phenylhydrazine
acetate and then add 0-2 ml. (0-21 g.) of benzaldehyde. Cork the
flask securely and shake the contents vigorously. A yellow crystal-
line mass of the hydrazone soon begins to separate. Allow to
stand for 15 minutes, with occasional shaking, and then filter the
solid product at the pump, wash first with very dilute acetic acid
and then with water, and finally drain thoroughly. Recrystallise
the material from rectified or methylated spirit, the benzaldehyde
phenylhydrazone being thus obtained in fine colourless needles,
m.p. 157°: yield, 0-4 g.

Hydrobenzamide. (C6H6CH)3N2.
Benzaldehyde reacts with ammonia to give hydrobenzamide, in accordance
with the equation:
3C6H6CHO + 2NH1 = (0,H8CH)8N1 + 3H,O
This behaviour is in marked contrast to that of the aliphatic aldehydes, which
230 PRACTICAL ORGANIC CHEMISTRY
usually give direct addition products with ammonia, although polymerisation
CH8CHO + HNH, = CH8CH(OH)NH2 > (C 2 H 7 ON) 8
may follow. Formaldehyde is an exception among the aliphatic aldehydes, since
it undergoes condensation with ammonia to give hexamethylene tetramine (or
6CH2O + 4NH 8 - (CH 2 ) 6 N 4 + 6K2O
urotropine (p. 379), a reaction which resembles that given by benzaldehyde.
Required: Benzaldehyde, 5 ml.; concentrated ammonia, 50 ml.
Place 5 ml. of benzaldehyde in a wide-necked stout-walled bottle of
about ioo ml capacity (a conical flask is too fragile for this purpose)
and add 50 ml. of concentrated (d, 0-880) ammonia solution. Cork the
bottle securely, shake vigorously, and then allow to stand for 24 hours,
by which time the layer of benzaldehyde at the bottom of the bottle
will have been converted into a hard mass of hydrobenzamide. (If
after 24 hours the crude hydrobenzamide is still syrupy, shake the
mixture vigorously and allow to stand for another hour, when the
conversion will be complete.) Break up the solid pellet with a strong
spatula, filter at the pump, wash with water and drain thoroughly.
Recrystallise from ethanol: methylated spirit should not be used, as it
contains sufficient water to cause partial hydrolysis back to benzal-
dehyde and ammonia. Hydrobenzamide is obtained as colourless
crystals, m.p. 101° (and not 110° as frequently quoted): yield, 4 g.
Hydrobenzamide is readily hydrolysed even by cold dilute acids.

Benzylidene-aniline. C6H5CH:NC6H5.(Semi-microScale.)
Aldehydes undergo condensation with primary amines with the elimination
of water to give compounds known as SchifT's Bases, which can also be used to
characterise aldehydes. Benzaldehyde for example condenses readily with
C 6 H 5 CHO I H 2 NC 6 H 5 -> C 6 H 5 CHiNC 6 H 5 + H 2 O

aniline to give benzylidene-aniline. In other cases in which the condensation


is not so rapid, it may be hastened considerably by the addition of a trace of
anhydrous zinc chloride.
Required: Benzaldehyde, i ml.; aniline, i ml.
Mix i ml. of benzaldehyde and i ml. of aniline in a small
evaporating-basin, place the latter on a boiling water-bath and
stir the mixture gently with a glass rod. Globules of water soon
appear on the oily layer. After about 20 minutes place the basin in
ice-water, and stir the contents well, whereupon solidification
should rapidly occur. (If the material does not solidify, replace
the basin on the boiling water-bath for a further 10 minutes.)
Break up the solid material in the basin, transfer to a conical
flask, and recrystallise from rectified spirit. The benzylidene-
aniline is obtained as colourless crystals, m.p. 52°: yield, 0-8 g.
PREPARATIONS 231
Dibenzal-acetone. C6H5CHrCHCOCHiCHC6H5 (Claisen
Reaction). (Semi-micro Scale.)
When an ethanolic solution containing both acetone and two equivalents of
benzaldehyde is made alkaline with sodium hydroxide, rapid condensation
occurs with the formation of dibenzal-acetone, or dibenzylidene-acetone. This
2C 6 H 6 CHO + CH 3 COCH 3 = C 6 H 5 CH:CHCOCH:CHC 6 H 6 + 2H8O
Dibenzal-acetone.
is a particular example of the Claisen Reaction,* for Claisen showed that alde-
hydes under the influence of sodium hydroxide will condense with (i) another
aldehyde, or (ii) a ketone, with the elimination of water. Thus benzal-
dehyde will condense with (i) acetaldehyde to give cinnamic aldehyde, and
with (ii) one equivalent of acetone to give (mono) benzal-acetone. In these
(i) C 6 H 5 CHO + HCH2CHO = C 6 H 6 CHiCH CHO + H 2 O
Cinnamic aldehyde,
(ii) C 6 H 5 CHO 4- HCH 2 COCH 3 = C 8 H 6 CHtCHCOCH 3 + H 2 O
Benzylidene-acetone.
reactions it is probable that an intermediate hydroxy-compound is formed
(C6H6CH(OH)CH2CHO and C 6 H 6 CH(OH)CH 2 COCH 3 respectively) and
water is then lost from the unstable - CH(OH)CH 2 - group.
Required: Benzaldehyde, i ml.; acetone, 0-4 ml.; methylated
spirit, 10 ml.
Dissolve i ml. of benzaldehyde and 0-4 ml. of pure acetone in
10 ml. of methylated spirit contained in a conical flask or wide-
mouthed bottle of about 50 ml. capacity. Dilute 2 ml. of 10%
aqueous sodium hydroxide solution with 8 ml. of water, and add
this dilute alkali solution to the former solution. Shake the
mixture vigorously in the securely corked flask for about 10
minutes (releasing the pressure from time to time if necessary)
and then allow to stand for 30 minutes, with occasional shaking:
finally cool in ice-water for a few minutes. During the shaking,
the dibenzal-acetone separates at first as a fine emulsion which then
rapidly forms pale yellow crystals. Filter at the pump, wash well
with water to eliminate traces of alkali, and then drain thoroughly.
Recrystallise from hot methylated or rectified spirit. The
dibenzal-acetone is obtained as pale yellow crystals, m.p. 112°:
yield, 0-6 g.
Benzyl Alcohol, C6H5CH2OH9 and Benzoic Acid,
C6H5COOH. (Cannizzaro's Reaction).
When benzaldehyde is treated with a concentrated caustic alkali solution,
polymerisation occurs with the formation of benzyl benzoate, which then
* This Reaction should be carefully distinguished from the Claisen Conden-
sation, which is the condensation of an ester, under the influence of sodium
ethoxide, with (i) another ester, (ii) a ketone, or (iii) a nitrile, with the elimination
of alcohol. For details of this condensation, see Ethyl Acetoacetate, p. 264.
232 PRACTICAL ORGANIC CHEMISTRY
undergoes hydrolysis giving benzyl alcohol and the alkali salt of benzole acid.
The final result is equivalent to the reduction of one molecule of benzaldehyde
C 8 H 5 CHO + OHCC 6 H 6 = C 6 H 5 COOCH 1 C 6 H 6
C 6 H 6 COOCH 2 C 6 H 6 + KOH = C 8 H 6 CH 2 OH + C 8 H 6 COOK
to the corresponding alcohol, and oxidation of the second molecule to the corres-
ponding acid. The two products can be readily separated by treatment with
water, in which the potassium benzoate dissolves, whilst the benzyl alcohol
separates as an insoluble oil which can be removed by extraction with ether:
acidification of the residual aqueous solution by concentrated hydrochloric
acid then precipitates the benzoic acid.
This reaction is given by most aromatic aldehydes having the aldehyde
group directly joined to the benzene ring: it is also given by formaldehyde,
with the formation of methanol and formic acid. Other aliphatic aldehydes do
not give Cannizzaro's reaction under these conditions.
Required: Potassium hydroxide, 27 g.; benzaldehyde, 30 ml.
Dissolve 27 g. of potassium hydroxide* in 20 ml. of water
contained in a small beaker or conical flask, keeping the latter
partly immersed in ice-water to prevent the mixture from boiling
as the potash dissolves, and finally to ensure that the complete
solution is thoroughly cooled. Pour the cold solution into a stout-
walled bottle of about 250 ml. capacity, and add 30 ml. (31-5 g.)
of benzaldehyde; cork the bottle securely (a glass stopper must
not be used because the alkaline solution on standing would
cement it firmly in position) and then shake the mixture vigorously
until it has been converted into a thick emulsion, which may finally
coagulate into a heavy dough-like mass. Allow the product to
stand for at least 4 hours (preferably overnight), and then add
sufficient water (about ioo ml.) to dissolve all the solid matter
present. Pour the liquid into a separating-funnel, rinse out
the bottle with about 20 ml. of ether, and then add this ether to the
solution in the funnel. Shake the solution in order to extract the
benzyl alcohol with the ether, separate the lower aqueous solution,
and then repeat the extraction twice more, using about 20 ml. of
ether on each occasion. If the original reaction product has been
allowed to stand overnight, the ethereal solution of the benzyl
alcohol will be free from unchanged benzaldehyde: if it has been
allowed to stand for only about 4 hours, shake the united ether
extracts with a moderately concentrated solution of sodium bi-
sulphite to remove traces of benzaldehyde, and then shake the
* The cost of this preparation (particularly for large classes) can be appre-
ciably reduced by using a solution of 20 g. of sodium hydroxide in 25 ml. of
water, in place of the potassium hydroxide solution. In this case, however,
the product on standing overnight forms a very hard mass, which should be
dissolved in warm water. The yields of alcohol and acid are unchanged.
PREPARATIONS 233
ethereal solution in turn with dilute sodium hydroxide solution (to
ensure complete removal of the bisulphite) and lastly with a
small quantity of water. Finally, in either case, dry the ethereal
solution by shaking with powdered anhydrous potassium carbon-
ate, and then distil off the ether from the filtered solution, using
the usual apparatus for this purpose (p. 163): then replace the
water-condenser by an air-condenser and distil the benzyl alcohol
over a gauze, collecting the fraction of b.p. 200-207°. Benzyl
alcohol is a colourless liquid of b.p. 205° and d, 1-04: it is almost
odourless, and is only slightly soluble in water. Yield, 14 g.
To obtain the benzoic acid, add an excess of concentrated
hydrochloric acid carefully with stirring to the aqueous alkaline
solution remaining from the original extraction. When no further
precipitation of benzoic acid occurs, cool the solution (if percep-
tibly warm) in ice-water, and then filter at the pump. Wash the
benzoic acid thoroughly with cold water, drain, and then recrystal-
lise from a large volume of boiling water. Benzoic acid is obtained
as colourless crystals, m.p. 121°: yield, 19-20 g.
For reactions of benzyl alcohol, see p. 336, and of benzoic acid, p. 347.

Benzoin. C6H6CH(OH)COC6H5.
Many aromatic aldehydes (having the - CHO group joined directly to the
benzene ring) undergo polymerisation when heated with a solution of potassium
cyanide in aqueous ethanol. Thus benzaldehyde gives benzoin, a compound of
double function, since it contains both a secondary alcoholic and a ketonic
2C6H6CHO = C 6 H 5 CH(OH)COC 8 H 5
grouping. The reaction is probably due to the potassium cyanide undergoing
partial hydrolysis, generating hydrogen cyanide, which then adds on to the
benzaldehyde giving benzaldehyde cyanhydrin: the latter then reacts with

C 6 H 5 CH(OH)CN f HCOC 6 H 5 -> C 6 H 5 CH(OH)COC 6 H, -f HCX


unchanged benzaldehyde, giving benzoin and regenerating the hydrogen cyanide
Required: Potassium cyanide, 5 g.; ethanol, 50 ml.; benz-
aldehyde, 25 ml.
Add 5 g. of powdered potassium cyanide* to a mixture of
20 ml. of water and 50 ml. of ethanol contained in a 200 ml.
conical flask, and then add 25 ml. (26 g.) of freshly distilled
benzaldehyde. Fit the flask with a reflux water-condenser, and
boil the mixture gently on a water-bath for 30 minutes, a clear
solution being rapidly obtained. Then pour the solution into a
beaker and cool; the benzoin separates as a crystalline mass
* See footnote, p I Q I .
234 PRACTICAL ORGANIC CHEMISTRY
Filter at the pump, and wash well with water. (Yield, about 20
g.) Recrystallise a portion from hot methylated spirit, reserving
the remainder for the following preparation. Benzoin is a very
pale yellow (almost colourless) crystalline substance, m.p. 137°.

Benzil. C6H6CO-COC6H5.
The secondary alcohol group, - CH(OH) -, in benzoin is readily oxidised
to a ketone group, and thus benzil, a diketone, is obtained.
C 6 H 6 CH(OH)COC 6 H 6 + O = C 6 H 5 CO-COC 6 H 5 + H 2 O
For this purpose, the usual oxidising agent is nitric acid, which in these circum-
stances (i.e., in the absence of sulphuric acid) does not nitrate the benzene ring.
Owing to the nitrous fumes formed by the reduction of the nitric acid, the
experiment should be performed in a fume-cupboard.
Required: Benzoin, io g.; nitric acid, 25 ml.
Place io g. of powdered benzoin and 25 ml. of concentrated
nitric acid in a 150 ml. flask fitted with a reflux water-condenser,
and heat the flask on a boiling water-bath. A flask having a
ground-glass neck fitting directly to the condenser is best for this
purpose. If this is not available, fit the flask to the condenser by
means of a cork (not a rubber stopper) and clamp both flask and
condenser securely in position during the heacing on the water-
bath: the nitrous fumes rot the cork during the heating, and if
only one clamp is used, the flask may possibly slip away from the
condenser, or alternatively the latter may fall sideways under its
own weight. Continue the heating for i| hours, when the crys-
talline benzoin will have been completely replaced by the oily
benzil. Then pour the mixture into a beaker of cold water, when
on vigorous stirring the oil will crystallise into a yellow solid.
Filter off the latter at the pump, and wash thoroughly with water to
ensure complete elimination of acid. Recrystallise from methyl-
ated or rectified spirit. Benzil separates as clear yellow crystals,
m.p. 95°: yield, 9 g.
Benzil Osazone. C6H5C(:N.NHC6H5)C(:N.NHC6H5)C6H6.
(Semi-micro Scale.)
The ready oxidation of the secondary alcohol group in benzoin to a ketone
group is also shown by the action of phenylhydrazine, which when present in
excess first gives benzoin phenylhydrazone, C 6 H 5 CH(OH)C(:NNHC e H 5 )C 6 H 6 ,
then oxidises the latter to the ketone, C 6 H 5 COCONNHC 6 H 5 )C 6 H 6 , and
finally gives the diphenylhydrazone, i.e., the osazone of benzil, the complete
action being similar to the formation of glucosazone (p. 135). Benzil osazone
can therefore be prepared either (a) from benzoin or (6) directly from benzil, and
its constitution thus placed beyond doubt.
PREPARATIONS 235
Required: Benzoin, i g.; acetic acid, 15 ml.; phenylhydrazine, 2 ml.
(a) Dissolve i g. of powdered benzoin in 15 ml. of hot glacial
acetic acid contained in a boiling-tube, and add 2 ml. of phenylhydra-
zine. Heat the tube in a boiling water-bath for 20 minutes. The
osazone crystallises out either during the heating or when the tube is
removed from the bath and the contents stirred. Cool the tube
thoroughly in water, filter off the yellow crystals at the pump through a
small Buchner funnel, drain, and then wash thoroughly first with
glacial acetic acid and then with ethanol, in order to remove all traces of
the original mother-liquor. The benzil osazone is thus obtained as
fine yellow crystals, which when dry are pure. M.p. 225°. Yield, i g.
The osazone can be recrystallised from acetic acid, or (better) from
benzene, although the benzene solution may require seeding or scratch-
ing before crystallisation starts.
(b) Repeat the preparation, using i g. of benzil instead of i g.
of benzoin. The benzil osazone crystallises out readily in yellow
needles, usually after about 5 minutes' heating. Continue heating for
20 minutes, and then isolate as before. Yield, 1-4 g. Carry out a
mixed melting-point determination to show that the two products are
identical.

Benzilic Acid. (C6H5)2C(OH)-COOH.


When benzil is heated with potassium hydroxide solution, it undergoes a
"molecular rearrangement" with the formation of the potassium salt of benzilic
acid, or diphenyl-glycollic acid:
C 6 H 6 -CO-CO-C 8 H 6 + KOH > (CeH6)2C(OH)-COOK
This reaction applies to many i,2-diketones, and is termed the Benzilic Acid
Rearrangement. It provides a ready method for the preparation of disubstituted
a-hydroxy-carboxylic acids. When applied to a cyclic i,2-diketone, the ring
system is necessarily reduced by one carbon atom: for example, cyclohexan-i,2-
H2
H2r/>0 H2) |H2
I I + KOH
H2
H2 H2
dione gives the potassium salt of i-hydroxycyclopentane-carboxylic acid.
Required: Benzil, 5 g.; potassium hydroxide, 5 g.
Dissolve 5 g. of benzil in 15 ml. of boiling ethanol in a conical
flask fitted with a reflux water-condenser. Then add a solution
of 5 g. of potassium hydroxide in 10 ml. of water, and heat
the mixture (which rapidly develops a purple colour) on a
boiling water-bath for about 15 minutes. Cool and stir the solu-
tion, from which the potassium benzilate separates in fine crystals.
236 PRACTICAL ORGANIC CHEMISTRY
Filter the product at the pump, using an alkali-resisting filter-
paper, or a sintered glass filter-funnel. Wash the crystals on the
filter with a small quantity of ethanol to remove the purple
colour, and then drain thoroughly.
To obtain the free acid, dissolve the potassium salt in 50 ml. of
cold water, filter the solution if a small undissolved residue
remains, and then boil the clear solution gently whilst dilute
sulphuric acid is added until the separation of the acid is com-
plete. Cool the solution and filter off the pale orange-coloured
crystals of the benzilic acid: wash the crystals on the filter with
some hot distilled water, drain well, and then dry in a desiccator.
Yield of crude acid, 4 g. Recrystallise from benzene (about 50
ml.) to which a small quantity of animal charcoal has been added,
filtering the boiling solution through a preheated funnel fitted
with a fluted filter-paper, as the benzilic acid readily crystallises
as the solution cools; alternatively, recrystallise from much hot
water. The benzilic acid is obtained as colourless crystals,
m.p. 150°.

Cinnamic Acid. C8H6CHrCH-COOH. (Perkin's Reaction.)


Cinnamic acid is usually prepared by Perkin's reaction, benzaldehyde being
heated with sodium acetate in the presence of acetic anhydride. It is probable
that the benzaldehyde and the acetic anhydride combine under the catalytic
action of the sodium acetate, and the product then readily loses water to give
mono-benzylidene acetic anhydride (A). The latter, when subsequently

C 6 H 5 CHO -f HCH 2 CO-O-OCCH 3 -^ C 15 H 5 CH(OH)CH 2 CO-O-OCCH 3


CeH 5 CH(OH)CH 2 CO-O-OCCH 3 - >H 2 O + C 6 H 5 CHiCHCOO-OCCH 3 (A)
heated with sodium carbonate solution, undergoes hydrolysis to sodium cinna-
mate and acetate.
C 6 H 8 CHiCHCO-O-OCCH 3 -h Na 2 CO, -> C 6 H 5 CHiCHCOONa
+ CH3COONa + CO 2
Although the cis-trans isomerism about the double bond is possible in
cinnamic acid, Perkin's reaction gives rise only to the stable trans form, of m.p.
133°, the cij form (known as a//o-cinnamic acid) being unstable and easily
converted to the trans form. In substituted ethylene compounds, it is frequently
found that if the two groups joined to either of the double-linked carbon
atoms differ considerably in nature or in mass (e.g., in cinnamic acid, the
phenyl group and hydrogen atom on one carbon, or the hydrogen atom and
the - COOH group on the other carbon), then one isomeride is formed to the
almost complete exclusion of the other.
Required: Benzaldehyde, 20 ml.; acetic anhydride, 30 ml.;
anhydrous sodium acetate, 10 g.
PREPARATIONS 237
Place 20 ml. (21 g.) of benzaldehyde (freshly distilled to
ensure absence of benzoic acid), 30 ml. of acetic anhydride, and
10 g. of finely powdered anhydrous sodium acetate* in a ioo ml.
round-bottomed flask fitted with a water-condenser closed at the
top by means of a calcium chloride tube bent downwards (c/.
Fig. 61, p. 105). Now heat the flask in an oil-bath at 175-180°
for 8 hours: the mixture boils vigorously under reflux and white
particles separate in the liquid. Pour the mixture whilst still hot
into ioo ml. of water contained in a round-bottomed flask (of
about i litre capacity) which has previously been fitted for steam-
distillation. Now add with vigorous shaking a saturated aqueous
solution of sodium carbonate until a drop of the liquid withdrawn
on a rod turns red litmus-paper a distinct blue. (Sodium hydrox-
ide must not be used for this purpose, as it may generate benzoic
acid by the Cannizzaro reaction from any unchanged benzal-
dehyde.) Now steam-distil the solution until unchanged benzal-
dehyde has been removed and the distillate is no longer turbid.
Cool the residual solution until the small quantity of insoluble
oily impurity has formed a semi-solid sticky mass, and then
filter at the pump. Acidify the clear filtrate by adding con-
centrated hydrochloric acid cautiously with vigorous stirring
until the evolution of carbon dioxide ceases and the precipitation
of cinnamic acid is complete. Cool if necessary in ice-water, and
then filter off the cinnamic acid, wash thoroughly with water, and
drain. Recrystallise from a mixture of 3 volumes of water and i
volume of rectified spirit: yield, 18 g. Cinnamic acid is thus
obtained as colourless crystals, m.p. 133°: it has a faint and
pleasant odour and is almost insoluble in cold water.
If in the above preparation 8 hours' continuous heating is
impracticable, the heating may be stopped after about 4 hours,
the mixture allowed to stand (e.g.> overnight) and the heating
then continued to make up the total period: in these circum-
stances the yield usually drops to about 15 g.
For reactions of cinnamic acid, see p. 353.
Ethyl Cinnamate. C6H6CH:CHCOOC2H6. Required: Cinnamic
acid, 20 g.; rectified spirit, 20 ml.
Cinnamic acid can be readily esterified by the Fischer-Speier method
without any risk of the addition of hydrogen chloride at the double
bond. Proceed precisely as for the preparation of ethyl benzoate (p. 104),
using 20 g. of cinnamic acid and 20 ml. of rectified spirit. When the
crude product is poured into water, a sharp separation of the ester is not
readily obtained, and hence the addition of about 10 ml. of carbon
tetrachloride is particularly desirable. Finally distil off the carbon
* Cf. p. 116 for preparation.
238 PRACTICAL ORGANIC CHEMISTRY
tetrachloride slowly from the dried product and then collect the ester as
the fraction boiling at 269-272°. Yield, 17 g.
Ethyl cinnamate is a colourless liquid of b.p. 271° and d, 1-05; it
possesses a pleasant and characteristic odour.

i,8-Diphenyloctatetrene.
C6H5 CH:CH(CH:CH)2 CHiCHC6H5.
This reaction illustrates one of the methods by which R. Kuhn synthesised
long polyene chains terminated at each end by phenyl groups.
When cinnamaldehyde, succinic acid and acetic anhydride are heated in the
presence of litharge (PbO), the aldehyde and the succinic acid condense to give
the dicarboxylic acid (I), which undergoes decarboxylation to give the pale
yellow crystalline i,8-diphenyloctatetrene (II). Kuhn has shown that as the
PhCH:CH-CHO + H2C CH, + OCH-CH:CHPh
I I
COOH COOH
I
PhCH:CH-CH:C C:CH-CH:CHPh
I i
COOH COOH (I)
I
PhCH:CH-CH:CH-CH:CH-CH:CHPh (II)
length of the polyene chain increases in such compounds, the colour steadily
darkens, and becomes red when the chain contains 9 double bonds.
Although a compound such as (II) could theoretically exist in a number of
geometrically-isomeric forms, only one form is produced in this synthesis: it is
almost certainly the trans form throughout the chain.
Required: Cinnamaldehyde, 16-3 ml. (18 g.); succinic acid,
8 g.; acetic anhydride, 18-5 ml. (20 g.); powdered litharge, 15 g.
For this preparation, the cinnamaldehyde must first be purified
by careful redistillation at the water-pump, and a fraction of
steady b.p. (e.g., I26°/I5 mm.) collected.
Prepare a mixture of the above compounds in the stated quan-
tities in a flask fitted with a reflux water-condenser. Shake the
mixture thoroughly, and then heat it in an oil-bath at 145-150°
for 3 hours. After about 10 minutes' heating, the mixture gives
a clear red solution which should be shaken occasionally during
the subsequent heating.
Allow the reddish-yellow solution to cool to about 40° and
then filter off at the pump the polyene which has separated:
this filtration should be performed as rapidly as possible to avoid
contamination with lead acetate, and a Buchner funnel of not
less than 6 cm. diameter should therefore be used to avoid
clogging the filter. Wash the crude production the filter with
PREPARATIONS 239
ca. 10 ml. of chloroform to remove sticky impurity. Weight of
crude dark yellow product, 3 g. Recrystallise from xylene or
from a much greater volume of chloroform. The i,8-diphenyl-
octatetrene is obtained as bright yellow crystals, m.p. 228°.
Yield, 2 g. If the preparation is carried out on a much larger
scale, mechanical stirring of the heated mixture is advisable.
Since the octatetrene contains two -CH: CH-CH: CH- units, it will readily
combine with two molecules of maleic anhydride and other adducts by the
Diels-Alder reaction (p. 292).

Benzoic Acid, C6H5COOH, from Benzyl Chloride,


C6H5CH2Cl.
When an aromatic compound having an aliphatic side chain is subjected to
oxidation, fission of the side chain occurs between the first and second carbon
atoms from the benzene ring, the first carbon atom thus becoming part of a
carboxyl ( -COOH) group. For example:
C8H5CH8 > C8H6COOH C 6 H 5 CH 2 CH 3 > C 6 H 6 COOH
C6H6COCH1 > C8H6COOH C6H6CH:CH'COOH > C6H6COOH

COOH Cl
COOH
Such oxidations are frequently important for determining the position of a
side chain relative to other substituents in the benzene ring. The oxidation is
usually carried out with a mixture of potassium permanganate and sodium
carbonate in aqueous solution, or alternatively with dilute nitric acid (1:1 by
volume). These oxidations are, however, often very slow, particularly if the
side chain is a simple alkyl group: to overcome this difficulty, the alkyl group
is frequently chlorinated in order to increase its susceptibility to oxidation.
Thus the side chain in toluene, C6H5CH3, is only very slowly oxidised by either
of the above reagents, whereas that in benzyl chloride is rapidly oxidised: this
rapid oxidation is due to the fact that with an aqueous oxidising agent, the
benzyl chloride is first hydrolysed to benzyl alcohol, which then undergoes
the normal oxidation of a primary alcohol to the corresponding carboxylic
acid.
In the following preparation, the oxidation of benzyl chloride instead of
toluene is therefore given in order to reduce the time required. It should be
borne in mind, however, that the procedure is otherwise independent of the
nature of the side chain.
Required: Anhydrous sodium carbonate, 5 g.; potassium
permanganate, 10 g.; benzyl chloride, 5 ml.; sodium sulphite,
ca. 20 g.
To 200 ml. of water contained in a 500 ml. bolt-head flask
240 PRACTICAL ORGANIC CHEMISTRY
add in turn 5 g. of anhydrous sodium carbonate, 10 g. of
potassium permanganate, and finally 5 ml. (5-5 g.) of benzyl
chloride. Fit the flask with a reflux water-condenser, and boil
the mixture gently for i-i£ hours, i.e., until the reaction is com-
plete and the liquid running down from the condenser contains
no oily drops of unchanged benzyl chloride. During this boiling,
the permanganate is slowly reduced, and manganese dioxide
separates as a dark brown precipitate. Now cool the flask, and
add concentrated hydrochloric acid (about 50 ml.) cautiously
until the mixture is strongly acid, and all the benzoic acid has been
precipitated. Then add a 20% aqueous solution of crystalline
sodium sulphite (about ioo ml.) slowly with shaking until the
manganese dioxide is completely dissolved* and only the white
precipitate of benzoic acid remains. When the mixture is quite
cold, filter off the benzoic acid at the pump, and wash well with
water. Recrystallise from boiling water. The benzoic acid is
obtained as colourless needles, m.p. 121°: yield, about 4-5 g.
Benzoyl Chloride. C6H5COCL
One of the general methods for the preparation of acid chlorides is the action
of phosphorus pentachloride on the corresponding carboxylic acid:
RCOOH + PCl6 = RCOCl + POCl, + HCl
One disadvantage of this method is that it is sometimes difficult to separate
the acid chloride sharply from the phosphorus oxychloride by fractional dis-
tillation, and unless the boiling-points of these two substances are fairly
wide apart, traces of the oxychloride will occasionally pass over in the vapour
of the acid chloride. If, however, thionyl chloride is used instead of phosphorus
RCOOH + SOCl, = RCOCl + SO2 + HCl
pentachloride, this difficulty does not arise, as the acid chloride is now the only
liquid product of this reaction.
Required: Benzoic acid, 20 g.; thionyl chloride, 15 ml.
For this preparation, which must be performed in the fume-cupboard,
assemble the apparatus shown in Fig. 67(A). C is a 150 ml. distilling-
flask, to the neck of which is fitted a reflux single-surface water-
condenser D, closed at the top E by a calcium chloride tube. The side-
arm of C carries a cork F which fits the end E of the condenser for
subsequent distillation. The side-arm of C is meanwhile plugged by a
small rubber cork, or by a short length of glass rod. (Alternatively, use
the ground-glass flask and condenser (Fig. 22 (A) and (c), p. 43), and
* Sulphur dioxide reacts with manganese dioxide giving the soluble colour-
less manganese dithionate: MnO« -f 2SO1 = MnS 2 O 8 . Some manganese
sulphate is also formed: MnS8O6 -f MnO1 = 2MnSO 4 . In the presence of
hydrochloric acid, some of the dioxide is also reduced to the monoxide, which
then dissolves to give manganous chloride, MnCl1.
PREPARATIONS 241
for the later distillation use the adaptor and receiver (Fig. 23(A) and (B),
p. 45) in place of G in Fig. 67(6).)
Place 20 g. of dry powdered benzoic acid in C, add 15 ml.
(25 g., i.e., a 30% excess) of thionyl chloride and some frag-
ments of porcelain, and then clamp the apparatus on a boiling
water-bath as shown so that no liquid can collect in the side-arm
of C. Heat for one hour (with occasional gentle shaking), by
which time the evolution of gas will be complete. Cool the flask C,
detach the condenser
and fit it to the side-
arm for distillation,
using a 360° thermo-
meter for the neck of
C. To the lower end
of the condenser fit a
small conical flask G
(Fig. 67(6)) by a cork
carrying also a cal-
cium chloride tube.
In place of the con-
ical flask G, a small
Buchner flask may be
used with the calcium
chloride tube fitted
to the side-arm, but
in either case a dupli- (B)
cate flask for the
second fraction FIG. 67.
should be available.
Now distil the contents of C by heating carefully over a gauze.
A small initial fraction of unchanged thionyl chloride boiling at
78-80° comes over, and the temperature then rises rapidly to 194°.
Directly this happens, stop the distillation, allow the condenser
to drain thoroughly, and then replace G by the duplicate receiver.
Run the water out of the condenser so that it acts as an air-
condenser, and then continue the distillation. Collect the benzoyl
chloride as the fraction boiling at 194-198°. Yield, 19 g.
In the distilling-flask remains a very small high-boiling fraction of
benzoic anhydride (b.p. 366°), formed by the dehydrating action of the
thionyl chloride on the benzoic acid :
2C 6 H 5 COOH + SOCl 2 = (C 6 H 5 CO) 2 O -f SO2 -f 2HCl.
Benzoyl chloride is a colourless highly refractive liquid, having
242 PRACTICAL ORGANIC CHEMISTRY
b.p. 198° and d, 1-21. It has a very irritating odour, and its
vapour causes copious watering of the eyes. Benzoyl chloride has
similar properties to acetyl chloride, but is much less reactive,
e.g., it is only slowly hydrolysed by cold water to benzoic acid and
hydrochloric acid. It is largely used as a reagent for identifying
alcohols and primary and secondary amines (see below).
For reactions of benzoyl chloride, see p. 364.
3,5-Dinitrobenzoic Acid. (NO2)2C6H3COOH.
Required: Benzoic acid, 50 g.; cone, sulphuric acid, 230 ml;
fuming nitric acid, 73 ml.
Dissolve 50 g. of benzoic acid in 230 ml. of concentrated sul-
phuric acid in a litre flask fitted with a ground-glass reflux water-
condenser. (Rubber or cork must not be used.) Now add a few
ml. of the fuming nitric acid down the condenser, shake the flask
well and keep it cool by immersion in ice-water. Continue the
intermittent addition of nitric acid (about 10 ml. at a time) with
continuous shaking and cooling: a great deal of heat is evolved on
each addition and a clear yellow solution is obtained. When the
addition is complete, add a few pieces of unglazed porcelain and
transfer the flask to a cold water-bath. Raise the temperature of
the latter gradually during 45 minutes to 100°. [At 70-80° the
reaction sometimes tends to become vigorous, and should then
be moderated by careful immersion in cold water.] Maintain
the mixture at 100° for 15 minutes, with occasional shaking, and
then transfer the flask to an oil-bath at 100°. Raise the tempera-
ture gradually to 130° during 30 minutes and then maintain it
between 130° and 140° for i hour. Thus the total period of
heating is 2\ hours during which the temperature is gradually
raised to 140°. Now cool the flask: crystals of 3,5-dinitrobenzoic
acid begin to separate at about 90°. When cold pour the contents
of the flask in 3-4 1. of ice-water. Filter off the crystals on a
Buchner funnel and wash with water. After drying, the crystals
have m.p. 204° (yield, 49 g.) and are sufficiently pure for the
preparation of 3,5-dinitrobenzoyl chloride (see below).
If desired, the 3,5-dinitrobenzoic acid may be recrystallised
from water as almost colourless rhombs, m.p. 204°.
3,5-Dinitrobenzoyl Chloride. (NO2)2C6H3COCL
This preparation illustrates the use of phosphorus pentachloride for the
preparation of acyl chlorides: in this case no difficulty is experienced in separa-
ting the 3,5-dinitrobenzoyl chloride from the phosphorus oxychloride formed
simultaneously (cf. p. 240), because the former is readily isolated as a crystalline
PREPARATIONS 243
solid. This acyl chloride is used extensively for the preparation of crystalline
derivatives of alcohols, phenols, amines and amino-acids (cf. pp. 335, 338 381)
Required: 3,5-Dinitrobenzoic acid, 15 g.; phosphorus penta-
chloride, 17 g.
Assemble in a fume-cupboard the apparatus shown in Fig. 6y(A).*
Place 15 g. of 3,5-dinitrobenzoic acid and 17 g. of phosphorus
pentachloride in the flask C, and heat the mixture in an oil-bath for i J
hours. Then reverse the condenser as shown in Fig. 6y(B), but replace
the calcium chloride tube by a tube leading to a water-pump, the neck
of the reaction-flask C being closed with a rubber stopper. Now distil
off the phosphorus oxychloride under reduced pressure by heating the
flask C in an oil-bath initially at 25-30°, increasing this temperature
ultimately to 110°. Then cool the flask, when the crude 3,5-dinitro-
benzoyl chloride will solidify to a brown crystalline mass. Yield,
16 g., i.e., almost theoretical. Recrystallise from carbon tetrachloride.
The chloride is obtained as colourless crystals, m.p. 66-68°. Yield,
13 g. Further recrystallisation of small quantities can be performed
using petrol (b.p. 40-60°). The chloride is stable almost indefinitely if
kept in a calcium chloride desiccator.
The Schotten-Baumann Reaction. I. Benzoylation.
Acetylation (i.e., the introduction of the acetyl group, CH3CO -) as a means
of characterising and identifying hydroxy-compounds and primary and secon-
dary amines has already been described (p. 107). It is, however, frequently
preferable to introduce an aromatic acyl group (such as the benzoyl group,
C 6 H 6 CO -) for this purpose rather than the acetyl group. Benzoylation has
two important advantages over acetylation: (a) acetyl chloride and acetic
anhydride are so readily hydrolysed that acetylation has usually to be per-
formed in absence of water; benzoyl chloride, C6H6COCl, is so slowly hydro-
lysed by water that benzoylation can be carried out freely in an aqueous
medium; (6) benzoyl derivatives usually have higher melting-points than the
corresponding acetyl compounds, and are usually much less soluble in most
solvents: they can therefore be more readily crystallised. Moreover, benzoyl
compounds are all insoluble in water and can thus be readily isolated from the
crude reaction product, whereas acetyl compounds (particularly of the ali-
phatic amines) are frequently soluble in water and therefore difficult to isolate.
In the Schotten-Baumann method of benzoylation, the hydroxyl- or amino-
compound (or a salt of the latter) is dissolved or suspended in an excess of 10%
aqueous sodium hydroxide solution, a small excess (about 10% more than the
theoretical amount) of benzoyl chloride is then added and the mixture vigor-
ously shaken. Benzoylation proceeds smoothly under these conditions, and
the solid benzoyl compound, being insoluble in water, separates out. The
sodium hydroxide then hydrolyses the excess of benzoyl chloride, giving sodium
C6H5COCl + 2NaOH = NaCl + C6H8COONa + H t O
chloride and benzoate, which remain in solution.
* P. 241.
244 PRACTICAL ORGANIC CHEMISTRY
Thus phenol when subjected to the Schotten-Baumann reaction first dis-
solves in the sodium hydroxide to give sodium phenoxide, which then undergoes
C 6 H 5 COCl + NaOC 6 H 5 -> C 6 H 5 COOC 6 H 5 + XaCl
bcnzoylation to give phenyl benzoate. An aqueous suspension of aniline
similarly gives benzoyl-aniline, or phenyl-benzamide (frequently called benz-
C 6 H 5 NHH + ClCOC 6 H 5 -> C 6 H 5 NHCOC 6 H 5 -f HCl
anilide); whilst monomethylaniline gives benzoyl-monomethylaniline or
C 6 H 5 N(CH 3 )H -f ClCOC 6 H 3 -> C 6 H 5 X(CH 3 )COC 6 H 5 + HCl
A 7 -methylphenylbenzamide. Tertiary amines clearly cannot react in this way.
When these benzoyl compounds separate in the course of the Schotten-
Baumann reaction, they frequently occlude traces of unchanged benzoyl
chloride, which thus escapes hydrolysis by the alkali: it is advantageous there-
fore to recrystallise the benzoyl compounds whenever possible from ethanol or
methylated spirit, since these solvents will esterify the unchanged chloride
and so remove the latter from the recrystallised material.
Occasionally benzoyl chloride gives a product which does not crystallise
well: in such cases the difficulty may frequently be overcome by using
p-nitrobenzoyl chloride, NO 2 C 4 H 4 COCl, or 3,5-dinitrobenzoyl chloride,
(p. 240), which usually give highly crystalline derivatives.

Phenyl Benzoate. C6H5COOC6H5. (Semi-micro Scale.)


Required: Phenol, i g.; benzoyl chloride, 2 ml.
Dissolve i g. of phenol in 15 ml. of 10% sodium hydroxide
solution contained in a strong wide-mouthed bottle of about 50
ml. capacity. Then add 2 ml. of benzoyl chloride, cork the
bottle securely and shake the mixture vigorously for 15 min-
utes. At the end of this time the reaction should be complete, and
a solid product obtained, although a faint smell of unchanged ben-
zoyl chloride may possibly still persist, owing to slight occlusion
by the solid product, absorption by the cork, etc. Filter off the
solid ester at the pump, breaking up any lumps on the filter with
a spatula, and then wash thoroughly with water and drain.
Recrystallise the crude ester from methylated spirit: for this
purpose use a quantity of the hot solvent approximately twice the
minimum required for complete solution, in order to ensure that
the phenyl benzoate does not separate until the temperature of the
solution has fallen below the melting-point of the ester: filter
the hot solution if necessary through a funnel preheated by the
filtration of some boiling solvent. Phenyl benzoate is thus
obtained as colourless crystals, m.p. 69°: yield, 1.2-1-5 £•
Hydrolysis of Phenyl Benzoate. The hydrolysis of phenyl benzoate
(and of phenol esters generally) is of particular interest, because both products
PREPARATIONS 245
of hydrolysis are acidic in type: if the hydrolysis is carried out with sodium
C6H1COOC6H6 + H8O = C6H6COOH -f C 8 H 5 OH
hydroxide, both compounds remain in solution as their sodium derivatives.
They may, however, be separated by acidifying the solution (in order to liberate
both acid and phenol) and then adding an excess of sodium carbonate. The
benzoic acid readily displaces carbonic acid giving sodium benzoate, whereas
the phenol is too weakly acidic to give a similar reaction and so remains free
in solution (cf. p. 347).
Boil a mixture of i g. of phenyl benzoate and 15 ml. of 10% aqueous
sodium hydroxide* in a 50 ml. conical flask under reflux until the
molten ester has completely disappeared (about i hour). During
the boiling, a small quantity of unchanged ester may have volatil-
ised in the steam and crystallised again in the condenser: therefore
pour about 3 ml. of 10% sodium hydroxide solution down the condenser
to dislodge this ester, and continue the boiling for a further 10 minutes
until the solution is clear. Cool the solution in ice-water, and then add
dilute sulphuric acid with stirring until a faint but permanent precipitate
of benzoic acid is produced (test with litmus-paper to ensure that solu-
tion is acidic). Now add dilute sodium carbonate solution with vigorous
stirring until the precipitate is just redissolved and the solution is
definitely alkaline to litmus-paper. Extract the solution twice with
ether, dry the united ethereal extracts with potassium carbonate, and
after filtering, distil off the greater part of the ether. Pour the remainder
whilst hot into an evaporating-basin; the phenol will crystallise
when the residual ether has evaporated. Confirm the identity of the
phenol by the tests given on p. 337. Meanwhile, add hydrochloric acid
to the aqueous solution from the ether extraction: the sodium car-
bonate is first neutralised and the benzoic acid then precipitated.
Filter off the benzoic acid at the pump, wash with water, and then
recrystallise from boiling water. Benzoic acid is obtained as colourless
crystals, m.p. 121°.

Benzanilide (Benzoyl-aniline). C8H6NHCOC6H6.


(Semi-micro Scale.)
Required: Aniline, i ml.; benzoyl chloride, 1-5 ml.
Add i ml. (1*04 g.) of aniline to 15 ml. of 10% aqueous
sodium hydroxide solution contained in a wide-necked bottle as
before, and then add 1-5 ml. (1-7 g.) of benzoyl chloride, and
shake vigorously for 15-20 minutes. The mixture becomes
warm, and the crude benzoyl derivative separates as a white
* If about io ml. of ethanol are added to the mixture, the time required for
complete hydrolysis is reduced to about 20 minutes, and any volatilised ester
which tends to collect in the condenser is redissolved and returned to the flask.
When hydrolysing an unknown ester (p. 353) for identification purposes,
however, it is often best to omit the ethanol to avoid confusion.
246 PRACTICAL ORGANIC CHEMISTRY
powder, or, if the shaking has not been sufficiently vigorous, as
small pellets: when the reaction is complete, filter off the product
at the pump, break up any pellets with a spatula on the filter, and
then thoroughly wash with water and drain. Recrystallise the
benzanilide from hot methylated spirit: for this purpose use
rather more of the hot solvent than the minimum required for
complete solution, and filter the latter through a funnel pre-
heated by the filtration of some of the boiling solvent, as the
benzanilide may crystallise rapidly as the solution cools: it is
only slightly soluble in cold methylated spirit. Benzanilide is
thus obtained as colourless crystals, m.p. 163°: yield, 1-6 g.
For reactions of benzanilide, see p. 379.

Hydrolysis of Benzanilide. For this hydrolysis, it is necessary


to use 70% sulphuric acid (see Hydrolysis of Acetanilide, p. 108).
Add i g. of benzanilide to 10 ml. of 70% sulphuric acid, and boil the
mixture gently in a small flask under a reflux water-condenser for 30
minutes. Hydrolysis will now be complete, but much of the benzoic
acid will have vaporised in the steam and then solidified in the conden-
C 6 H 5 NHCOC,H 6 +H 2 0+H 2 S0 4 =C 6 H 5 NH 2 ,H 2 S0 4 +C 6 H 6 COOH
ser. Therefore remove the flask, run the water out the condenser
jacket, and then pour about io ml. of hot water down the inner tube,
which is held vertically over a beaker. The benzoic acid is thus dis-
lodged and largely dissolved. Then add the hot solution from the
flask, and cool in ice-water. Benzoic acid rapidly crystallises, but at
this dilution the aniline sulphate, although sparingly soluble, does not
separate. Filter off the benzoic acid, wash with water, drain, and apply
the tests given on p. 347. Note the m.p. (121°). With the filtrate,
perform the tests for aniline (pp. 372-373).
Benzyl />-Nitrobenzoate. NO2C6H4COOCH2C6H5.
(Semi-micro Scale.)
A crystalline derivative of benzyl alcohol cannot be obtained by using
benzoyl chloride, because the benzyl benzoate, C 6 H 5 COOCH 2 CeH 5 , so obtained
has m.p. 18°, and is thus usually liquid: the present preparation illustrates
therefore the use of a substituted benzoyl chloride (/>-nitrobenzoyl chloride,
m.p. 75°) in order to obtain a crystalline derivative of suitably high m.p.
Required: Benzyl alcohol, i ml.; p-nitrobenzoyl chloride, 1-9 g.
Place i ml. of benzyl alcohol in a boiling-tube and add 6 ml. of 10%
sodium hydroxide solution: add also 6 ml. of water to moderate the
subsequent reaction, otherwise the rise in temperature may cause
hydrolysis of some of the ester produced. Now add 1*9 g. of finely
powdered p-nitrobenzoyl chloride, and shake the well-corked tube
vigorously. The mixture becomes warm, and the solid ester rapidly
PREPARATIONS 247
separates, the reaction being complete after about 5 minutes' shaking.
Filter the ester at the pump, wash with dilute sodium hydroxide
solution, then thoroughly with water, and drain. Recrystallise from
methylated spirit, allowing the hot solution to cool slowly at first:
finally cool in ice-water. The benzyl p-nitrobenzoate separates in
colourless crystals, m.p. 84°. Yield, r6 g.

Methyl 3,5-Dinitrobenzoate. (NO2)2C6H3COOCH3.


(Semi-micro Scale.)
The reaction between 3,5-dinitrobenzoyl chloride and compounds containing
the OH, NH 2 , or NH groups is very rapid, and therefore is particularly suitable
for identification purposes (cf. pp. 335, 338, 381). It is usual to have sodium
hydroxide present during the reaction with phenols and amino-acids, but this is
not necessary with alcohols if they are dry.

Required: 3,5-Dinitrobenzoyl chloride, i g.; methanol, 2-5 ml.


Place i g. of powdered 3,5-dinitrobenzoyl chloride in a small conical
flask, add 2-5 ml. of dry methanol, and warm on a water-bath until
the solid has dissolved. Cool and filter off the 3,5-dinitrobenzoate
which has separated. Recrystallise from ethanol* or petroleum (b.p.
60-80°). The ester separates in colourless crystals, m.p. 108°, Yield,
0-6 g.

The Schotten-Baumann Reaction. IL Sulphonylation.


The Schotten-Baumann reaction may also be carried out, using, for example,
benzene sulphonyl chloride, C8H5SO2Cl (i.e., the acid chloride of benzene
sulphonic acid, C 6 H 6 SO 2 OH) in place of benzoyl chloride, and similar deriva-
tives are obtained. Thus when phenol is dissolved in an excess of 10% sodium
hydroxide solution, and then shaken with a small excess of benzene sulphonyl
C 6 H 5 SO 2 Cl + NaOC 6 H 5 -> C 6 H 5 SO 2 OC 6 H 5 + NaCl
chloride, phenyl benzenesulphonate, a crystalline ester, is readily formed, and
the excess of the sulphonyl chloride then undergoes hydrolysis by the alkali,
giving the soluble sodium benzenesulphonate. A suspension of aniline in
sodium hydroxide when similarly treated with benzenesulphonyl chloride gives
benzenesulphonyl-aniline, whilst monomethylaniline gives benzenesulphonyl-
methylaniline: alternatively, these two compounds may be regarded as being
C 6 H 5 NHH + ClSO 2 C 6 H 5 -> C 6 H 5 NHSO 2 C 6 H 5 + HCl

C 6 H 5 N(CH 3 )H + ClSO 2 C 6 H 5 -> C 6 H 5 N(CH 3 )SO 2 C 6 H 5 + HCl


mono-and di-substituted derivatives of benzenesulphonamide, C 6 H 5 SO 2 NH 2
and thus termed benzenesulphonphenylamide, and benzenesulphon-
methylphenylamide respectively. Sulphonylation, like benzoylation, can there-
* Esters of one alcohol should not normally be recrystallised from another
alcohol. In the above case, however, no interchange of alkyl groups occurs on
rapid recrystallisation.
248 PRACTICAL ORGANIC CHEMISTRY
fore be used to obtain crystalline derivatives of hydroxyl compounds, and also of
primary and secondary amines: tertiary amines cannot undergo sulphonylation.
There is, however, one important difference between the benzoyl and the
sulphonyl derivatives of amines. It has been shown that primary and secondary
amines, when treated with benzoyl chloride, give mono- and di-substituted
derivatives of benzamide, and when treated with benzenesulphonyl chloride,
give similar derivatives of benzene sulphonamide. A carboxylic acid amide,
such as benzamide, possesses only very weak amphoteric properties (p. 120),
and is therefore practically neutral, and its derivatives are consequently insoluble
in dilute aqueous solutions of alkalis or acids. A sulphonic acid amide, such as
benzenesulphonamide, is devoid of basic properties, but has its acidic properties
correspondingly increased, and therefore each of the hydrogen atoms in the
-NH 1 group can in turn show marked acidic properties. It follows that
sulphonamides and their mono-substitution derivatives are definitely acidic and
will therefore dissolve freely in sodium hydroxide solution, although they arc
insoluble in acids: their di-substitution derivatives, having no acidic hydrogen
atoms, are neutral and therefore insoluble in both alkalis and acids.
The acidic properties of sulphonamides and their mono-substitution deriva-
tives are particularly well illustrated in the alkyl-substitution compounds,
which by reason of these properties can be prepared by two distinct methods.
Thus mono- and di-ethylamine, when subjected to the Schotten-Baumann
reaction using benzenesulphonyl chloride, give benzenesulphonethylamide,
and benzenesulphondiethylamide respectively. These compounds can also
CeH6SO1Cl + HNHC1H6 = C6H6SO1NHC8H5 + HCl
C6H6SO8Cl + HN(C8H6), = C6H6SO8N(C1H6),, -f HCl
be prepared from benzenesulphonamide by direct substitution. If an
ethanolic solution of the sulphonamide is treated with sodium ethoxide, the
sulphon-sodio-amide is formed and may crystallise out: if this compound is
then heated with ethyl bromide or iodide, the sulphonethylamide (A) is
formed. The latter still retains an acidic hydrogen atom and therefore, when
NaOC2H5 C2H6I
C-H4SO1NH2 * C 6 H 5 SO 2 NHNa > CeH6SO1NHC1H1 (A)
treated in ethanolic solution with sodium ethoxide, gives the sulphon-sodio-
NaOC1H6 C8H6I
CgH8SO1NHC1H5 ^C8H6SO1NNaC1H5 *C,H6SO,N(C,H,)« (B)
cthylamide, which when heated in turn with ethyl iodide, gives the neutral
sulphon-diethylamide (B).
Hinsberg has based a method of separating primary, secondary and tertiary
amines upon the solubility of mono-substituted sulphonamides in sodium hy-
droxide solution If, for example, a mixture of aniline, monomethylaniline and
dimethylaniline is shaken with benzenesulphonyl chloride in the presence of an
excess of sodium hydroxide solution, the aniline gives benzenesulphonyl-aniline,
C9H1NHSO1CcH6, which, being acidic, remains dissolved in the alkaline
solution. The monomethylaniline gives benzenesulphonyl-methylaniline,
CtH5N(CH»)SO|CfHt, which, being neutral, is insoluble and therefore separates
out. The dimethylaniline is unaffected. When the tulphonylation is complete.
PREPARATIONS 249
the unchanged dimethy!aniline can therefore be recovered by steam-distillation.
The reaction product is then cooled and the insoluble sulphonyl-methylaniline
filtered off. The filtrate is then acidified, and the sulphonyl-aniline thus precipi-
tated. Hydrolysis of these two sulphonyl compounds then regenerates the
secondary and primary amines respectively.
Although benzenesulphonyl chloride has for simplicity been used in the
above discussion, toIuene-/>-suIphonvl chloride, CH 3 C 6 H 4 SO 2 Cl, is more fre-
quently used in the laboratory, owing to its much lower cost, the latter being
due in turn to the fact that toluene-/>-sulphonyl chloride is a by-product in the
commercial preparation of saccharin. Toluene-p-sulphonyl chloride is a
crystalline substance, of m.p. 68°: the finely powdered chloride will, however,
usually react readily with amines in the Schotten-Baumann reaction; it does
not react so readily with alcohols, but the reaction may be promoted consider-
ably by first dissolving the chloride in some inert water-soluble solvent such as
acetone.
Phenyl Toluene-/?-sulphonate. CH 3 C 0 H 1 SO 2 OC 0 H,.
(Semi-micro Scale.)
Required: Phenol, 0-4 g.; 10% sodium hydroxide, 2-5 ml.;
toluene-p-sulphonyl chloride, 0-9 g,; acetone, 4 ml.
Dissolve 0-4 g. of phenol in 2-5 ml. of 10% aqueous sodium
hydroxide solution contained in a 25 ml. conical flask, and then
add a solution of 0-9 g. of toluene-p-sulphonyl chloride in 4 ml.
of cold acetone: cork the flask securely and shake it vigorously for
15-20 minutes. When the mixed solutions are first shaken, a fine
emulsion forms and the mixture becomes warm: on continued
shaking (which prevents the emulsion from separating into two
well-defined layers) the fine oily drops crystallise as the temperature
falls, and when the shaking is complete, a crop of small heavy
crystals will have separated from the clear supernatant liquid.
Now cool the flask in water, and then pour the contents into about
25 ml. of water, finally washing out the flask to remove any
crystals adhering to the sides. Filter the well-stirred aqueous
mixture at the pump, wash the crystals thoroughly with water,
and drain. Recrystallise the product from methylated spirit,
of which about 12 ml. will be required. Phenyl toluene-p-
sulphonate is thus obtained as colourless crystals, m.p. 95°: yield,
0-7 g.
Separation of a Mixture of Aniline, Monomethylaniline,*
and Dimethylaniline.t Hinsberg's Method.
The principle of this method has been explained above. The reaction is
best carried out in a wide-necked 250 ml. conical flask for which a cork having
the usual two deli very-tubes for steam-distillation is available: when the
* Strictly termed JV-methylaniline.
t Strictly termed A T ,A r -dimethylaniline.
250 PRACTICAL ORGANIC CHEMISTRY
•ulphonylation is complete, the reaction product can then be steam-distilled
without transference to another vessel.
Required: Aniline, 4 ml.; monomethylaniline, 4 ml.; dimethyl-
aniline, 4ml.; toluenc-p-sulphonyl chloride, 16 g.
Prepare a mixture containing 4 ml. of each of the above three
amines. Place the mixture in the conical flask, add 60 ml. of
10 % sodium hydroxide solution, and also 60 ml. of water to
moderate the subsequent reaction. Add 16 g. of finely powdered
toluene-p-sulphonyl chloride, cork the flask securely and shake
the contents vigorously for 20-30 minutes: the mixture becomes
warm, and a fine emulsion of the unchanged dimethylaniline and
the molten sulphonyl-methylaniline forms in the alkaline solution.
Finally the temperature falls towards the end of the above period
of shaking. Now replace the cork by the steam-distillation
fitting, and steam-distil the reaction mixture until fine drops of
dimethylaniline can no longer be detected in the distillate leaving
the condenser. Then stop the distillation, and cool the reaction
mixture by shaking the flask in a stream of cold water under the
tap, in order to ensure that the sulphonyl-methylaniline solidifies
in small particles and not in one large hard lump.
Extract the dimethylaniline by shaking the distillate in a
separating-funnel with a few ml. of ether, and then dry the
ethereal solution over potassium carbonate: distil the filtered
ethereal solution from a small distilling-flask (e.g., Fig. 36, p. 63)
with the usual precautions, and finally the dimethylaniline, b.p.
193°. Yield, almost theoretical.
Meanwhile, filter the original cold reaction product at the
pump, and wash the sulphonyl-methylaniline on the filter first
with 10 % sodium hydroxide solution (to ensure complete re-
moval of the sulphonyl-aniline) and then with water: drain
thoroughly. Recrystallise from ethanol: toluene-p-sulphonyl-
methylaniline, C 6 H 6 N(CH 3 )SO 2 C 6 H 4 CH 3 , is thus obtained as
colourless crystals, m.p. 95°: yield, 7-5 g.
Finally, add an excess of concentrated hydrochloric acid slowly
with stirring to the alkaline filtrate remaining from the original
reaction product. As the solution becomes acid, the sulphonyl-
aniline separates as a thick sticky syrup which, when stirred,
rapidly crystallises. Cool the mixture in ice-water if necessary,
and then filter off the solid product at the pump, wash well with
water, and drain. Recrystallise from a mixture of 2 volumes of
ethanol and i volume of water: to prevent the sulphonyl-aniline
from separating as an emulsion, allow the hot solution to cool spon-
taneously (with occasional stirring) until crystallisation starts, and
PREPARATIONS 251
then cool in ice-water to complete the process. The toluene-
/>-sulphonyl-aniline, C 6 H 5 NHSO 2 C 6 H 4 CH 3 , when filtered and
drained is obtained as colourless crystals, m.p. 102°: yield, 6 g.
The aniline and the monomethylaniline can be obtained from
their respective sulphonyl derivatives by hydrolysis with 70%
sulphuric acid (preparation, p. 109), the mixture of the sulphonyl
compound and the acid being gently boiled under reflux: to
illustrate the separation of the three amines, however, this is not
necessary.
The chief disadvantage of Hinsberg's method is that partial hydrolysis
of the two sulphonyl amines by the sodium hydroxide may occur during the
steam-distillation: if, however, only a small excess of the hydroxide is used in the
sulphonylation, this hydrolysis becomes negligible, particularly as the sul-
phonyl amides are far less readily hydrolysed by alkalis than by acids. This
point does not arise in the separation of a similar mixture of aliphatic amines,
since all the lower members are soluble in water. Therefore if a mixture of
mono-, di- and tri-ethylamine were treated as above with toluene-£-sulphonyl
chloride, the sulphonyl morio-ethylamine, C 2 H 6 NHSO 2 C 6 H 4 CH 8 , and the
unchanged triethylamine would remain dissolved in the sodium hydroxide
solution, whilst the neutral sulphonyl diethylamine (C 2 H 5 ) 2 NSO 2 C e H 4 CH 3 ,
would separate, and could then be filtered off. Acidification of the filtrate would
then precipitate the sulphonyl monoethylamine, whilst the triethylamine
remained in solution as a salt of the acid. After filtering off the sulphonyl
monoethylamine, the filtrate could be made alkaline again, and the liberated
triethylamine steam-distilled off from the crude residual solution.

Toluene-/>-sulphonamide. CH3C6H4SO2NH2.
Toluene-/>-sulphonyl chloride reacts with aqueous ammonia to give the
CH 3 C 6 H 4 SO 2 Cl + HNH 2 -> CH 3 C 6 H 4 SO 2 NH 2 + HCl
sulphonamide, but the reaction is slow. A more rapid reaction may be obtained
by heating the sulphonyl chloride with ammonium carbonate, which dissociates
readily into carbon dioxide and ammonia, and converts the chloride almost
quantitatively into the amide.
Required: Toluene-p-sulphonyl chloride, 5 g.; ammonium
carbonate, 10 g.
Thoroughly mix 5 g. of toluene-p-sulphonyl chloride and
10 g. of ammonium carbonate by grinding together in a mor-
tar until a fine uniform powder is obtained. Then heat the
mixture in an evaporating-basin on a boiling water-bath for 15-20
minutes, stirring the mixture continuously with a glass rod mean-
while. Conversion of the chloride to the amide is now complete
and only a small quantity of unchanged ammonium carbonate
remains. Recrystallise the powder from about 120 ml. of boiling
252 PRACTICAL ORGANIC CHEMISTRY
water. Toluene-p-sulphonamide is thus obtained in colourless
crystals, m.p. 137°. Yield 4-2-4-4 g.
Toluene-p-sulphonamide is almost insolubb in cold water, but
dissolves readily in sodium hydroxide solution (as the sodium derivative)
and is immediately reprecipitated on the addition of strong acids. To
show the formation of the sodium derivative, dissolve about 0-2 g. of
metallic sodium in about io ml. of ethanol, cool the solution, and then
add it to a solution of i g. of the sulphonamide in 20 ml. of cold ethanol.
On shaking the mixture, fine white crystals of the sodium derivative,
CH1C4H6SO1NHNa, rapidly separate, and may be obtained pure by
filtering at the pump, and washing first with a few ml. of ethanol, and
then with ether.
Toluene-p-sulphonchloro-sodio-amide ("Chloramine-T"),
CH3C0H4SO >NNaCl,3HoO, and Toluene-/) -sulphon-dichloro-
amide (" Dichloramine-T "), CH3C8H4SO2NCl2.
When toluene-/>-sulphonamide is dissolved in an excess of sodium hypo-
chlorite solution, toluene-/>-sulphon-chloro-sodio-amide is formed, and, being
soluble in water, does not crystallise unless concentrated solutions are used:
CH 8 C 6 H 4 SO 2 NH 2 + NaClO = CH8C6H4SO2NNaCl + H 2 O
This compound is similar in type to the sodium acet-bromoamide,
CH8CONNaBr, which is an intermediate compound in Hofmann's amine
synthesis (p. 127). If a weak acid (such as acetic acid) is now added to the
solution of the chloro-sodio-amide, the latter compound reacts with the hypo-
chlorous acid giving the sulphon-dichloro-amide, which being insoluble in
water, rapidly separates:
CH 3 C 8 H 4 SO 2 NNaCl + HOCl + CH3COOH
= CH 3 C 6 H 4 SO 2 NCl 2 + CH1COONa + H2O
When the sulphon-dichloro-amide is gently boiled with sodium hydroxide
solution, the reverse change occurs, and the chloro-sodio-amide crystallises out
at a suitable concentration:
CH 8 C 6 H 4 SO 2 NCl 2 + aNaOH = CH 3 C 6 H 4 SO 2 NNaCl + NaOCl + H2O
The chloro-sodio-amide can thus be made either directly from toluene-/>-sul-
phonamide or from the intermediate dichloro-amide. The chloro-sodio-amide
and the dichloro-amide arc known commercially as Chloramine-T and Dichlor-
amine-T respectively.
DICHLORAMINE-T. Dilute 8o ml. of freshly prepared zN sodium
hypochlorite solution (preparation, p. 525) with 8o ml. of water, and
then add with stirring 5 g. of finely powdered toluene-p-sulphonamide,
a clear solution being rapidly obtained. Cool in ice-water, and then
add about 50 ml. of a mixture of equal volumes of glacial acetic acid and
water slowly with stirring until precipitation is complete: the dichloro-
amide separates at first as a fine emulsion, which rapidly forms brittle
colourless crystals. Filter off the latter at the pump, wash well with
PREPARATIONS 253
water, drain thoroughly, and dry without delay either with drying-
paper or (better) in a desiccator. Yield, 6-8-7-0 g. (theoretical). The
dichloramine-T is thus obtained in a high state of purity: it may,
however, be crystallised with very little loss from 60-80° petrol, and
obtained as needles, m.p. 83°.
CHLORAMINE-T. (a) From Dichloramine-T. For this purpose use
dichloramine-T which has been prepared as above, and thoroughly
drained but not necessarily dried. Heat 40 ml. of 10% sodium hy-
droxide solution in a beaker over a gauze until the solution is almost
boiling, and then add the dichloramine-T in small quantities, stirring
the mixture gently after each addition until a clear solution is obtained.
When the addition is complete, cool the solution in ice-water, whereupon
the chloramine-T will rapidly separate in colourless crystals. Filter at
the pump, and drain thoroughly. Yield, 8 g. (almost theoretical). The
chloramine-T, which is now practically pure, may if desired be recrys-
tallised from a small quantity of hot water: dry the final product
with drying-paper or in a calcium chloride desiccator, as water of crystal-
lisation is readily lost over sulphuric acid or in a vacuum. Chlor-
amine-T has no definite m.p., for on heating it first loses water of
crystallisation and then decomposes vigorously at 175-180°.
(b) Direct from toluene-p-sulphonamide. Mix 45 ml. of the freshly
prepared 2Af sodium hypochlorite solution and 40 ml. of 10% sodium
hydroxide solution in a 200 ml. conical flask, and then add 5 g. of
finely powdered toluene-p-sulphonamide. Shake the corked flask
vigorously for 3-5 minutes, whereupon the sulphonamide will dissolve
and be largely replaced by white crystalline chloramine-T. Now warm
the mixture in the open flask until a clear solution is obtained (in order
to ensure removal of any dichloramine-T) and then cool. The chlor-
amine-T separates on slow cooling in needles, and on quick cooling in
characteristic leaflets. Filter, drain, and dry. Yield 7-5 g.
Both chloramine-T and dichloramine-T have marked antiseptic
properties, chloramine-T being most frequently used because of its
solubility in water. Aqueous solutions of chloramine-T can be used
either for external application, or for internal application to the mouth,
throat, etc., as chloramine-T in moderate quantities is non-toxic: its
aqueous solution can also be effectively used when the skin has come in
contact with many of the vesicant liquid " poison-gases," as the latter
are frequently organic sulphur or arsenic derivatives which combine
with or are oxidised by chloramine-T and are thus rendered harmless.
Both chloramine-T and dichloramine-T can be readily estimated, because
they liberate iodine from potassium iodide quantitatively in the presence of
CH 3 C 6 H 4 SOjNNaCI -f 2KI + 2CH3COOH
= CH,C.H 4 S0 2 NH 2 + NaCl + I, -f 2CH3COOK
CH 3 C 6 H 4 SO 2 NCl 8 -f 4 KI + 4CH8COOH
= CH1C6H4SO1NH, + 2HCl + 2!, 4- 4CH1COOK
254 PRACTICAL ORGANIC CHEMISTRY
acetic acid. For this purpose, a solution of a known quantity of chloramine-T
in water containing acetic acid, or dichloramine-T in acetic acid itself, is
diluted with an excess of potassium iodide solution, and the iodine is then
estimated by direct titration with standard sodium thiosulphate solution.

Aromatic Ketones.
Aromatic ketones may be divided into two classes:
(1) The true ketones, in which the >CO group is in the side chain, the most
common examples being acetophenone or methyl phenyl ketone, C6H8COCH3,
and benzophenone or diphenyl ketone, C4H6COC6H5. These ketones are
usually prepared by a modification of the Friedel-Crafts* reaction, an aromatic
hydrocarbon being treated with an acyl chloride (either aliphatic or aromatic)
in the presence of aluminium chloride. Thus benzene reacts with acetyl chloride
C 6 H 5 H + ClCOCH3 -> C 6 H 5 COCH 3 -f HCl
readily in these circumstances to give acetophenone.
A probable mechanism of the reaction is as follows:
+
CH8COCl -f AlCl8 -> CH3CO + AlCl4
(I)
The benzene nucleus is then attacked by the carbonium ion (I) (cf. attack by
+
NO a ion, p. 157): + +
C6H5H -f CH8CO -> CeH8COCH3 + H
followed by: +
H -f AlCl4 -> HCl -f AlCl8.

(2) The quinones, in which the carbon of the >CO group is part of the
ring; for this reason, the properties of the >CO group are sufficiently
modified to make the quinones quite distinct from the true ketones of class (i).
Quinones may often be prepared by direct oxidation of the corresponding
hydrocarbon: thus anthracene (A) on oxidation gives anthraquinone (B)
whilst phenanthrene (C) gives phenanthraquinone (D), these quinones being

examples of para and ortho quinones respectively. The specific term quinone
is usually applied to />-benzoquinone (F) which cannot easily be prepared by the
direct oxidation of benzene on a laboratory scale. It can, however, be readily
PREPARATIONS
prepared by the addition of a mild oxidising agent, 9H
such as ferric chloride, to an aqueous solution of
hydroquinone (E), a reaction which is readily revers-
ible by reducing agents such as sulphur dioxide: it is
also technically prepared by the more complicated
oxidation of compounds such as aniline.
The preparation of a member of each of the above classes of ketones is given
below.

Acetophenone. C6H6COCH3.
Required: Aluminium chloride, 30 g.; benzene, 75 ml.; acetyl
chloride, 20 ml.
Place 30 g. of anhydrous finely powdered aluminium chloride*
in a 300 ml. dry round-bottomed bolt-head flask, and add 75 ml.
of dry benzene (free from toluene). Fit a water-condenser to the
flask, and then in turn fit a small dropping-funnel securely in the
top of the condenser by means of a cork having a shallow V--
shaped groove cut vertically in the side to give open access to the
air. (Alternatively use the apparatus shown in Fig. 23(A), p. 45,
the outlet-tube A being closed with a calcium chloride tube.)
Cool the contents of the flask in a basin of cold water (ice-water
must not be used, in case the benzene crystallises): now place
20 ml. (22 g.) of acetyl chloride in the dropping-funnel, and
allow it to run slowly down the condenser into the flask, the latter
being shaken from time to time to ensure thorough mixing of the
contents. When all the acetyl chloride has been added, heat the
flask in a water-bath at 50° for i hour in order to complete the
reaction, a vigorous evolution of hydrogen chloride occurring
meanwhile. The heating should therefore be carried out in the
fume-cupboard, the dropping-funnel being replaced by a calcium
chloride tube, bent downwards as in Fig. 61, p. 105. Alternatively,
the heating may be carried out in the open laboratory, in which
case a delivery-tube should be securely fitted at one end to the
top of the condenser (or to the outlet-tube A in Fig. 23(A)), and
at the other end to the stem of an inverted glass filter-funnel, the
latter being placed in a beaker of water so that the rim dips just
below the surface: the hydrogen chloride is thus absorbed without
* Aluminium chloride is usually supplied by dealers either in stoppered
bottles or in sealed glass flasks. Great care should be taken in opening the sealed
flasks, as they frequently contain hydrogen chloride under considerable pressure.
The flask or tube should first be chilled in ice-water or ice-salt, and then
enveloped in a thick duster so that only the tip of the neck protrudes. A scratch
is made across the neck with a sharp file and the scratch then touched with the
hot end of a fine glass rod: the end of the neck may fly off with great violence
and should therefore be pointing in a safe direction.
256 PRACTICAL ORGANIC CHEMISTRY
risk of water "sucking back" through the tube into the reaction
mixture (c/. Fig. 62, p. 128).
When the heating is complete, cool the reaction mixture and
then pour it into 200 ml. of water contained in a flask of about
750 ml. capacity. Then cork the flask and vigorously shake it,
cooling in water if necessary: aluminium chloride and hydrogen
chloride are thus extracted by the water, whilst the acetophenone
remains dissolved in the benzene. Pour the mixture into a
separating-funnel and run off the lower aqueous layer: shake the
benzene solution with a dilute aqueous sodium hydroxide solu-
tion to ensure complete removal of hydrogen chloride, and again
separate the benzene and then dry it over calcium chloride for
about 15 minutes. Filter the dry solution and remove the ben-
zene by distillation. For this purpose fit a ioo ml. distilling-flask
containing some fragments of unglazed porcelain with a dropping-
funnel and a water-condenser: run a portion of the benzene solu-
tion into the flask, which is then heated on a sand-bath, the
remainder of the solution being added as the benzene distils over.
(Alternatively, the flask may be heated in a boiling water-bath,
since benzene will not readily distil from a flask heated on a
water-bath.) When almost all the benzene has been removed,
replace the dropping-funnel by a 360° thermometer, and the
water-condenser by a short air-condenser similar to that used in
the preparation of acetamide (p. 117). Then continue the distilla-
tion by careful heating over a gauze, and finally collect the aceto-
phenone as the fraction of b.p. 195-202°. Yield, 20 g. This frac-
tion should be collected directly into a weighed specimen-tube,
and should crystallise readily when the tube is cooled in ice-
water. If it does not crystallise, it should be redistilled.
Acetophenone is a colourless compound, having m.p. 20° and
b.p. 201°; except in cold weather it is therefore usually a liquid,
of d, 1-03. It has only a faint odour. Acetophenone was at
one time used medicinally under the name of hypnone as a
soporific, but for this purpose it has now been largely superseded
by other and more suitable drugs.
Acetophenone. (Semi-micro Scale.)
Required: Aluminium chloride, 3 g.; benzene, 7-5 ml.; acetyl chloride,
2 ml.
The student should first read the directions for the macro-scale
preparation above.
Place in a 25 or 50 ml. round-bottomed flask, 3 g. of finely powdered
anhydrous aluminium chloride and 7-5 ml. of dry benzene. Fit the
flask with a reflux water-condenser. Place the flask in a cold water-
PREPARATIONS 257
bath in a fume-cupboard and add slowly down the condenser, from a
calibrated dropping-tube, 2 ml. of acetyl chloride. Shake the flask
after each addition (about 0-5 ml. at a time). When all the acetyl
chloride has been added, fit the top of the condenser with a calcium
chloride tube bent downwards (cf. Fig. 61, p. 105), and heat the flask
in the water-bath at 50° for about 30 minutes. This usually suffices to
remove all the hydrogen chloride. When no more hydrogen chloride
is evolved pour the mixture into a ioo ml. flask containing 20 ml. of
water. Shake the flask vigorously: aluminium chloride and hydrogen
chloride are thus extracted by the water. Now pour the mixture into
a small separating-funnel and run off the lower aqueous layer. Wash
the benzene layer with dil. NaOH solution and again run off the lower
layer. Transfer the benzene layer to a small dry flask and dry with
anhydrous calcium chloride for 15 minutes. Transfer the dry benzene
solution (or a portion of it at a time) to a 10 ml. pear-shaped flask
(Fig. 37, p. 63). Distil off the benzene using preferably a vigorously
boiling water-bath. The benzene may, in this instance, be collected
directly in the boiling-tube C. When all the benzene has been dis-
tilled off, remove the boiling-tube C and the water-condenser D
from the side-arm of the flask. Now heat the flask A directly with a
small semi-micro Bunsen flame. Discard everything that comes over
below 195°. Collect the fraction boiling between 195° and 202° in a small
weighed specimen tube. Yield of acetophenone, 2 g. Immerse the
tube in ice-water and note that crystallisation takes place.
For reactions of acetophenone, see p. 345.
The student should note that ketones in class (i), i.e., those having the >CO
group in the side chain, will form additive compounds with sodium bisulphite
only if this >CO group is not directly joined to the benzene ring: acetophenone
therefore will not form such compounds, whereas benzyl methyl ketone,
C 6 H 6 CH 2 COCH 8 , will do so. Many quinones, particularly ortho quinones such
as phenanthraquinone, form additive compounds with sodium bisulphite.
Acetophenone Phenylhydrazone. CH3(C6H5)CiN-NHC6H5.
(Semi-micro Scale.)
Required: Acetophenone, i ml.; phenylhydrazine, 1-25 ml.; acetic
acid, 5 ml.
Dissolve i ml. (i g.) of acetophenone in 5 ml. of glacial acetic acid
contained in a boiling-tube for which a well-fitting cork is available.
Dissolve 1-25 ml. of phenylhydrazine in a mixture of 2-5 ml. of glacial
acetic acid and 2-5 ml. of water, and add this solution to that of the
acetophenone, at once corking and vigorously shaking the boiling-tube.
The mixture becomes slightly warm, and the phenylhydrazone rapidly
separates as colourless crystals. After 5 minutes' shaking, cool the tube
in cold water, and then filter the contents at the pump: wash the
crystals on the filter with dilute acetic acid and then with water. Recrys-
tallise the phenylhydrazone from ethanol (not from methylated spirit,
which causes decomposition) and dry thoroughly: m.p. 105°. Yield,
258 PRACTICAL ORGANIC CHEMISTRY
i .4 g. The phenylhydrazone, after standing for a few days, develops
a brown colour and ultimately decomposes.
Acetophenone similarly gives an oxime, CH 3 (C 6 H 5 )CiNOH, of m.p. 59°:
owing to its lower m.p. and its greater solubility in most liquids, it is not as
suitable as the phenylhydrazone for characterising the ketone. Its chief use
is for the preparation of i-phenyl-ethylamine, CH 3 (C 6 H 5 )CHNH 2 , which can
be readily obtained by the reduction of the oxime or by the Leuckart reaction
(p. 223), and which can then be resolved by ^-tartaric acid and /-malic acid into
optically active forms. The optically active amine is frequently used in turn for
the resolution of racemic acids.

Acetophenone Semicarbazone. CH3(C6H5)C :N NHCONH2.


(Semi-micro Scale.)
Aldehydes and ketones may frequently be identified by their semicarbazones,
obtained by direct condensation with semicarbazide (or ammo-urea),
NH a NHCONH a> a compound which is a monacidic base and usually available as
its monohydrochloride, NH 2 CONHNH 2 ,HCl. Semicarbazones are particularly
useful for identification of compounds (such as acetophenone) of which the
oxime is too soluble to be readily isolated and the phenylhydrazone is unstable:
moreover, the high nitrogen content of semicarbazones enables very small
quantities to be accurately analysed and so identified. The general conditions
for the formation of semicarbazones are very similar to those for oximes and
phenylhydrazones (pp. 93, 229): the free base must of course be liberated from
its salts by the addition of sodium acetate.
Required: Semicarbazide hydrochloride, i g.; anhydrous sodium
acetate, 0-9 g.; acetophenone, i ml.
Add first i g. of powdered semicarbazide hydrochloride and then
0-9 g. of anhydrous sodium acetate (or 1-25 g. of the crystalline acetate)
to 5 ml. of water, and warm gently until a clear solution is obtained.
Then add a solution of i ml. (i g.) of acetophenone in 5 ml. of rectified
spirit, and warm the mixed solutions gently on a water-bath for
CH3(C6H5)CO + H 2 N-NHCONH 2 ->
CH3(C6H5)C-N-NHCONH2 + H2O
15 minutes. The semicarbazone rapidly crystallises whilst the solu-
tion is still being heated. Finally cool, filter off the acetophenone
semicarbazone, wash thoroughly with water, and drain. Yield, 1-4 g.
(theoretical). The semicarbazone when dry has m.p. 197-198° and
is practically pure. It may be recrystallised from ethanol and obtained
as colourless crystals, m.p. 201°.
2,4-Dihydroxy-acetophenone. (Resacetophenone.)
(The Hoesch Reaction.)
The Hoesch Reaction is employed for the introduction of the - COR group
into the aromatic ring of phenol or a phenolic ether, and usually proceeds par-
ticularly readily with polyhydric phenols. If an ethereal solution of resorcinol (I)
PREPARATIONS 259
containing acetonitrile and zinc chloride is saturated with hydrogen chloride,
the acetonitrile forms the unstable but reactive imine, CH,-C(Cl) :NH, which

OH

CH 3 -CrNH (II) CH 3 -CO (III)

under the influence of the zinc chloride reacts with the resorcinol to give the
keto-imine (II). Keto-imines are basic and form salts, which are readily hydro-
lysed by aqueous acids to the corresponding ketone. The keto-imine (II) will
therefore separate initially as the chlorozincate, which on hydrolysis gives 2,4-
dihydroxy-acetophenone.
Required: Resorcinol, 5 g.; acetonitrile, 3*5 ml.; zinc chloride,
2 g.; anhydrous ether, 25 ml.
The Hoesch Reaction requires anhydrous conditions : therefore the
ether and the acetonitrile should each be dried and distilled before
use, and the resorcinol should be dried in a desiccator. Fit a 50 ml.
conical flask with a rubber stopper carrying a long inlet and a
short outlet tube, the latter being joined to a calcium chloride
guard-tube. Add in turn 25 ml. of ether, 5 g. of resorcinol and
2
'8 g- (3*5 nil.) of acetonitrile. Then rapidly pulverise 2 g. of
zinc chloride in a mortar (which preferably has been preheated in
an oven), transfer it to the mixture, and replace the stopper.
Clamp the flask securely in a basin of ice- water, and pass a stream
of dry hydrogen chloride (cf. p. 104) into the mixture, swirling the
latter occasionally. When the mixture is saturated, close the inlet
tube with a clip, and set the flask aside overnight. Then filter off
the chlorozincate of the imine (II) which has separated, and wash
it on the filter with a small quantity of ether. For hydrolysis, add
the chlorozincate to 50 ml. of dilute hydrochloric acid, and boil
the mixture under reflux for 30 minutes. Cool the clear solution,
filter off the 2,4-dihydroxy-acetophenone which separates, and
(after drying) recrystallise it from toluene; drain thoroughly and
dry in a desiccator over paraffin shavings (p. 20): cream-coloured
crystals, m.p. 145-146°. Yield, 3-5-4*0 g.
co
Anthraquinone. /
CH(6
\)C,H .
4 4

Anthracene is oxidised by chromium trioxide, CrO1, to anthraquinonc. As


the reaction is carried out in solution, a solvent is required which will dissolve
both the anthracene and the chromium trioxide, and at the same time be
26o PRACTICAL ORGANIC CHEMISTRY
unaffected by the vigorous oxidising action of the latter compound: acetic acid
fulfils these conditions admirably.
Required: Anthracene, 10 g.; acetic acid, 150 ml.; chromium
trioxide, 20 g.
Assemble an apparatus precisely similar to that used for the
preparation of acetophenone (p. 255), viz., a 500 ml. bolt-head
flask having a reflux water-condenser, into the top of which is fitted
a ioo ml. dropping-funnel by means of a cork having a V-shaped
groove cut vertically in the side to allow escape of air. (Alterna-
tively, use the apparatus shown in Fig. 23(A), p. 45.) Place 10 g.
of finely powdered anthracene and ioo ml. of glacial acetic
acid in the flask, mix thoroughly by shaking and then heat the
flask over a gauze so that the acetic acid boils gently under
reflux, and the greater part of the anthracene goes into solution.
Then dissolve 20 g. of chromium trioxide in 15 ml. of water,
add 50 ml. of glacial acetic acid, and pour the well-stirred mixture
into the dropping-tunnel. Now allow the chromium oxide solu-
tion to run drop by drop down the condenser at such a rate that
the total addition takes about 40 minutes. As the oxidation
proceeds, the anthracene dissolves up completely in the boiling
acetic acid. When the addition of the chromium oxide solution
is complete, continue the boiling for a further 20 minutes, and
then allow the solution to cool somewhat before pouring it into a
large excess (about 500 ml.) of cold water. The crude anthra-
quinone separates as a greenish-grey powder. Stir the mixture
vigorously in order to wash out as much acetic acid and chromium
derivatives as possible from the anthraquinone, and then filter off
the latter under gentle suction of the pump, wash it thoroughly on
the filter with hot water, then with a hot dilute solution of sodium
hydroxide, and finally with much cold water, before draining it
well. Dry the anthraquinone as completely as possible by
pressing it between several thick sheets of drying-paper. Yield,
i o-11 g. (almost theoretical).
Anthraquinone sublimes readily on being heated, and may easily
be obtained in a high state of purity by this method. Assemble the
apparatus shown in Fig. 10, p. 23. Place about half of the crude
product in the small evaporating-basin, and first warm the latter
gently over a gauze (using a very small flame) in order to dry the
product completely: when the evolution of steam is no longer
perceptible, place over the basin a filter-paper through which a
number of small holes (about 2 mm. in diameter) have been
pierced upwards. Then place in turn a cold dry filter-funnel (of
slightly smaller diameter than the basin) over the filter-paper,
PREPARATIONS 261
and heat the basin rather more strongly than before, at the same
time protecting the apparatus from draughts. After a few
minutes, the vapour of the anthraquinone passes through the
holes, and condenses on the upper surface of the filter-paper
and on the walls of the funnel in beautiful long yellow needles:
these are pure and have m.p. 277°. During the process of
sublimation, adjust the rate of heating so that the anthraquinone
is slowly yet steadily volatilised, but the funnel does not become
more than slightly warm.
Recrystallise the remaining half of the crude anthraquinone
from boiling acetic acid, using animal charcoal: filter the hot
solution through a Buchner funnel which has been preheated by
the filtration of some of the boiling solvent, as the anthraquinone
crystallises rapidly as the solution cools. Cool the filtrate in cold
water and then filter at the pump, drain, wash with methylated
spirit and dry. Yield, 4-5 g.

Anthraquinone. (Semi-micro Scale.)


Required. Anthracene, I g.; chromium trioxide, 2 g.; glacial acetic acid, 15 ml.
Dissolve i g. of anthracene in 10 ml. of glacial acetic acid and place in 50 ml.
bolt-head flask fitted with a reflux water-condenser. Dissolve 2 g. of chromium
trioxide in 2 ml. of water and add 5 ml. of glacial acetic acid. Pour this solution
down the condenser, shake the contents of the flask and boil gently for 10
minutes. Cool and pour the contents of the flask into about 20 ml. of cold
water. Filter off the crude anthraquinone at the pump, wash with water, drain
well and dry. Yield, i g. Purify by recrystallisation from glacial acetic acid or
by sublimation using the semi-micro sublimation apparatus (Fig. 35, p. 62, or
Fig. 50. P- ?o).
For reactions of anthraquinone, see pp. 370.
Anthraquinone is of great technical importance, as many of its
derivatives form valuable dyes: notable among these are the hydroxy-
derivatives (alizarin, etc.), the amino-derivatives (indanthrene, etc.) and
the sulphonic acids.

co-Dimethylaminopropiophenone Hydrochloride.
C6H5COCH2CH2N(CHg)2. (The Mannich Reaction.)
The Mannich Reaction involves the condensation of formaldehyde with
ammonia or a primary or secondary amine and with a third compound containing
a reactive methylene group: these compounds are most frequently those in which
the methylene group is activated by a neighbouring keto group. Thus when
acetophenone is boiled in ethanolic solution with paraformaldehyde and
dimethylamine hydrochloride, condensation occurs readily with the formation of
C.H.COCH, + H1CO + (CH^)1NH1HCl -* C 4 H,COCH,CH a N(CH,) t ,HCl
262 PRACTICAL ORGANIC CHEMISTRY
cd-dimethylaminopropiophenone hydrochloride. The reaction therefore affords
a ready synthesis of certain keto-amines.
It will be clear that the above reaction, if carried out with ammonia would give
first a primary amine, and if performed with a primary amine would give a second-
ary amine. Furthermore, if the above reaction were carried out with monomethyl-
(A) C 6 H 6 COCH 2 CH 2 NH(CH 8 ). (CeH6COCH,CH2)2NCH, (B)
amine hydrochloride, the initial product would be the hydrochloride of
G>-methylaminopropiophenone (A), but this compound could react again to give
the compound (B). In the reaction described below, such secondary reactions
do not occur.
Required: Acetophenone, 5 g.; paraformaldehyde, 1-25 g.;
dimethylamine hydrochloride, 3-5 g.
NOTE. Dimethylamine hydrochloride is a deliquescent substance:
the sample if damp must be dried in a vacuum desiccator and then
rapidly weighed before use.
Add 5 ml. (5 g.) of acetophenone, 1-25 g. of finely
powdered paraformaldehyde, and 3-5 g. of dry dimethylamine
hydrochloride to 8 ml. of absolute ethanol, and then boil the
mixture under reflux for 1-5 hours. Filter the solution (which
is now almost entirely clear) through a preheated filter-funnel,
and cool the filtrate in ice-water with stirring. The co-di-
methylamino-propiophenone hydrochloride rapidly separates as
white crystals; filter off the crystals at the pump and recrystallise
from a small quantity of ethanol: m.p. 155-156°. Yield, 2-5 g.

2,4-Dinitrophenylhydrazine. (NO 2 ^C 6 H 3 NHNH 1 .


2,4-Dinitrophenylhydrazine is a very important reagent for the identification
of aldehydes and ketones (pp. 342, 346). It is readily prepared from chloro-
2,4-dinitrobenzene (I). In the latter compound the chlorine is very reactive in
NO2
OH~ ^ VTX^ "V^1-1 (n)

NO2
NH, ^.^.T/y V^-VIWT /TIT^

(D
NH 2 -NH 2
-NH 2 (IV)

marked contrast to the extremely unreactive chlorine atom in chlorobenzene


(p. 391). This high reactivity of the chlorine atom is caused by the presence
of the two (ortho and para) nitro groups in the ring. Chloro-2,4-dinitrobenzene
is readily converted by dilute alkali into 2,4-dinitrophenoI (II) and by ammonia
PREPARATIONS 263
into 2,4-dinitroaniline (III). Similarly it reacts with one molecular equivalent of
hydrazine to give 2,4-dinitrophenylhydrazine (IV).
Required: Chloro- 2,4-dinitrobenzene, 10 g.; hydrazine hydrate,
8 ml. (64% w/w); dioxan,* 50 ml.
Dissolve 10 g. of chloro- 2,4-dinitrobenzenefin 50 ml. of dioxan
in a 250 ml. conical flask. Dilute 8 ml. of hydrazine hydrate
with an equal volume of water and add this slowly with shaking
to the dioxan solution, keeping the temperature between 20°
and 25°. Heat under reflux for 10 minutes to complete the
reaction and then add 5 ml. of ethanol and heat again for 5
minutes. Cool and filter off the orange 2,4-dinitrophenylhydra-
zine. Recrystallise the dry product from ethyl acetate: m.p. 200°
(decomp.). Yield, 7 g.
Preparation of 2,4-Dinitrophenylhydrazones. 2,4-Dinitrophenyl-
hydrazine is much more reactive than phenylhydrazine towards aldehydes and
ketones: consequently a compound having a carbonyl group of low reactivity
may often readily give a 2,4-dinitrophenylhydrazone, although the unsubsti-
tuted phenylhydrazone is difficult to prepare. Furthermore, 2,4-dinitrophenyl-
hydrazones usually have lower solubilities and higher melting-points than the
corresponding unsubstituted phenylhydrazones, and therefore separate from
solution and crystallise far more readily.
On the other hand, the two nitro groups make 2,4-dinitrophenylhydrazine a
very weak base, and it has therefore to be used in reasonably concentrated acid
solution.
Two solutions are recommended for use:
Reagent A. Dissolve 0-5 g. of the powdered dinitrophenylhydrazine
in a mixture of 8o ml. of concentrated hydrochloric acid and ioo ml. of
distilled water by gently heating the mixture on a water-bath. Cool the
solution and add 120 ml. of water. If necessary, filter the pale yellow
solution.
Reagent B. Suspend i g. of the powdered dinitrophenylhydrazine in
30 ml. of stirred methanol and cautiously add 2 ml. of concentrated sul-
phuric acid. If necessary, filter the solution whilst it is still warm and
cool the filtrate.
Both reagents should be stored in a cool place and preferably in the
dark. They should_be stable for several weeks, but ultimately give a
brown deposit.
Reagent A is particularly useful for the treatment of the lower
aliphatic aldehydes and ketones which are soluble in water (cf. acetalde-
hyde, p. 342; acetone, p. 346). The Reagent is a very dilute solution of
the dinitrophenylhydrazine, and therefore is used more to detect the pre-
sence of a carbonyl group in a compound than to isolate sufficient of the
hydrazone for effective recrystallisation and melting-point determination.
* Dioxan should be manipulated with care, for the vapour is toxic.
f Care must be taken when dealing with this substance as it can cause derma-
titis and also irritate the respiratory system.
264 PRACTICAL ORGANIC CHEMISTRY
Reagent B is valuable for use with aldehydes or ketones which are
insoluble in water, and therefore unsuitable for treatment with Reagent
A (cf. benzaldehyde, p. 342; benzophenone, p. 346). It is much more
concentrated than A, and consequently can be more readily used for
the isolation and purification of the required hydrazone.
Use. If the substance under investigation is soluble in water, dissolve
about 0*1 g. in 1-2 ml. of water, and add 5-10 ml. of Reagent A. On
shaking for a few minutes, with scratching if necessary, the yellowish-
orange hydrazone will usually separate: if this does not occur, warm the
solution gently in a hot water-bath for 5-10 minutes.
If the substance under investigation is insoluble in water, dissolve
about OT g. in a minimum of methanol or ethanol, with heating if
necessary, and then add 0-5-1 ml. of Reagent B: then proceed as above.
Precautions, (i) The above tests must be carried out with discretion. If the
substance is only moderately soluble in the solvent selected, and a comparatively
large volume of the latter is required, the consequent dilution of the acid in the
reagent may cause the separation of the free 2,4-dinitrophenylhydrazine (al-
though this is more likely to happen with Reagent B than with A). Furthermore,
if the compound under investigation should have basic properties, the neutralisa-
tion of part of the acid in the reagent may have the same result.
(2) 2,4-Dinitrophenylhydrazones usually separate in well-formed crystals.
These can be filtered at the pump, washed with a diluted sample of the acid in
the reagent used, then with water, and then (when the solubility allows) with a
small quantity of ethanol: the dried specimen is then usually pure. It should,
however, be recrystallised from a suitable solvent, a process which can usually
be carried out with the dinitrophenylhydrazones of the simpler aldehydes and
ketones. Many other hydrazones have a very low solubility in most solvents, and
a "recrystallisation" which involves prolonged boiling with a large volume of
solvent may be accompanied by partial decomposition, and with the ultimate
deposition of a sample less pure than the above washed, dried and unrecrystal-
lised sample.

Ethyl Acetoacetate. CH3COCH2COOC2H6. (Claisen


Condensation.)
Ethyl acetoacetate is a tautomeric substance which at room temperature
exists as an equilibrium mixture of the keto and enol forms, the latter form
being present to the extent of about 7%.
CH 3 COCH 2 COOC 8 H 5 ^ CH,C(OH):CHCOOC2H5
keto enol
It is readily prepared by the action of metallic sodium on dry ethyl acetate.
The reaction, which occurs only in the presence of a trace of ethanol, is complex,
but may be considered (in effect) as a condensation of two molecules of ethyl
acetate under the influence of sodium ethoxide, the sodium derivative of the
enol form being thus obtained. Clearly, only a trace of ethanol is thus initially
CH 3 COOEt + HCH 2 COOC 2 H 5 -f C 2 H 5 ONa ->
CH,C(ONa):CHCOOCtH§ +C1HjOH
PREPARATIONS 265
required. Treatment of the crude sodium derivative with a weak acid, e.g.,
dilute acetic acid, then gives the normal equilibrium mixture of the keto and
enol forms.
This preparation was discovered independently by Geuther (1863) and by
Frankland and Duppa (1865). The reaction was subsequently investigated in
detail and so widely extended by Claisen that it has become solely a specific
example of the more general process known as the Claisen Condensation.*
Claisen showed that an ester under the influence of sodium ethoxide would not
only condense with itself (as in the preparation of ethyl acetoacetate), but also
with (i) another ester, (ii) a ketone, if of formula RCH 2 COR, (iii) a nitrile, if of
formula RCH 2 CN, in each case with the elimination of alcohol. Examples of
these modifications are:
(i) C 6 H 5 COOC 2 H- HCH 2 COOC 2 H, -.C 6 H 3 COCH 2 COOC 2 H 5 - C 2 H 5 OH
Ethyl benzoatc Ethyl acetate Ethyl benzoylacetate.
(ii) CH 3 COOC 2 H 5 • HCH 2 COCH 3 — CH 3 COCH 2 COCH 3 ! C 2 H 3 OH
Ethyl acetate Acetone Acetyl-acetone.
(iii) C 2 H 5 OOC-COOC 2 H 5 - HCH 2 CX - C 2 H 5 OOC-COCH 2 CN ! C 2 H ,OH
Ethyl oxalate Acetonitrile Ethyl p-cyanopyruvate.
Many other examples of the Claisen Condensation will be found in textbooks
of theoretical organic chemistry.
The mechanism of the Claisen Ester condensation has been suggested along
the following lines:
CH 3 -CO 2 -Et +"OEt -> CH 2 -CO 2 -Et + EtOH

tf/ /- /O"
CH3-C / CH 2 -CO 2 -Et -> CH 3 -C - CH 2 -CO 2 -Et
X X
OEt OEt

CH3-CH2-CO2-Et -> CH 3 -C - CH 2 -COo-Et

O O
Il Il
CH 3 -C - CH 2 -CO 2 -Et + EtCT-* CH3-C - CH-CO 2 -Et + EtOH
I
CT
CH 3 -C=- CH-CO 2 -Et
Thus the sodio derivative (I) of the enol form of ethyl acetoacetate is obtained.
This mechanism can clearly apply also to the condensation of an ester with a
suitable ketone or nitrile, as in the above reactions (ii) and (iii) respectively.
* This Condensation should not be confused with the Claisen Reaction,
which is the condensation of an aldehyde with (i) another aldehyde, or (ii) a
ketone, under the influence of sodium hydroxide, and with the elimination of
•water. For details, see Dibenzal-acetone, p. 231.
266 PRACTICAL ORGANIC CHEMISTRY

Required: Ethyl acetate, 200 ml.; sodium, 15 g.; saturated


brine, 200 ml.
The ethyl acetate used in the preparation must first be dried.
For this purpose place about 200 ml. of ethyl acetate over granular
calcium chloride, shake thoroughly and allow to stand, preferably
overnight: then filter through a fluted filter-paper directly into
a distilling-flask fitted with a water-condenser and distil carefully
over a gauze. Use rubber stoppers or ground-glass joints for the
distillation apparatus, as bark corks contain appreciable quantities
of water.
Fit a 750 ml. bolt-head flask (also by a rubber stopper) to a
reflux water-condenser closed at the top by a calcium chloride
tube: ensure that flask and condenser are quite dry. Place 150
ml. of the dried ethyl acetate in the flask and add 15 g. of
sodium. The sodium for this purpose should preferably be added
in the form of wire directly from a sodium press (Fig. 55, p. 82):
alternatively the sodium may be added as thin slices, but in this
case each slice should be quickly pressed between drying-paper
before being added to the acetate to remove the wet film which
may have formed during the weighing and cutting of the metal.
Now heat the mixture on the water-bath, or (preferably) at 100°
in an oil-bath or an electric heater. Very little reaction occurs
whilst the acetate is still cold, but on warming a vigorous
reaction ensues and hydrogen is evolved. Continue heating until
a clear pale brown liquid entirely free from metallic sodium is ob-
tained—this usually requires 2-2J hours* heating, depending
largely on the initial condition of the sodium. Then cool thor-
oughly and add dilute acetic acid (i :i by volume) cautiously with
shaking until the liquid is just definitely acid to litmus-paper;
the addition of the acid first causes the formation of a semi-solid
white mass which redissolves to a clear solution as the mixture
becomes acid. Pour the solution into about 200 ml. of cold almost
saturated brine contained in a separating-funnel and shake the
mixture vigorously. The ethyl acetoacetate separates sharply
above the brine solution. Run off the lower layer of brine and
then transfer the ester to a conical flask; add some powdered
anhydrous sodium sulphate, and allow to stand for about 30
minutes with occasional shaking.
Meanwhile fit up a Claisen flask (of about 175 ml. capacity)
with a fine capillary and thermometer (see Fig. ia(A), p. 29),
taking care that the range of temperature of 7O°-ioo° is not
obscured by the cork. Then filter the crude ester at the pump
PREPARATIONS 267
using a Buchner funnel and flask, quickly drain the residue of
sodium sulphate in the funnel, and then rinse out the conical
flask with a few ml. of the original dried ethyl acetate, filtering the
latter through the sodium sulphate residue into the ester below.
Pour the latter into the Claisen flask, add some unglazed porcelain
and, temporarily discarding the capillary and thermometer, cork
the necks of the flask, connect it to a water-condenser and then
place it in a boiling water-bath. The greater part of the un-
changed ethyl acetate now distils over. When distillation ceases,
remove the flask, replace the capillary and thermometer, and fit
an apparatus for vacuum-distillation to the Claisen flask: for this
purpose the Perkin triangle apparatus (Fig. 14, p. 31), or that
shown with a "pig" (Fig. 23(F), p. 46), is preferable, but the
more simple apparatus shown in Fig. ia(A), p. 29, gives good
results. When a steady low pressure is attained in the apparatus,
heat the Claisen flask in an oil-bath, increasing the temperature
of the bath cautiously so that the distillation proceeds slowly.
The boiling-point of the distillate rises slowly as the low-boiling
impurities come over first, and finally becomes almost constant
as the ethyl acetoacetate distils. Therefore ensure by slow dis-
tillation that the low-boiling impurities pass over as completely
as possible before the ethyl acetoacetate starts to distil; if the
apparatus shown in Fig. i2(A) is used, the receiver must of course
be changed at this stage. The distillation of the acetoacetate can
readily be recognised from the following boiling-points, 73°/15
mm., 82°/2O mm., 87°/3O mm., 92°/4O mm., and a fraction boil-
ing over a range of 3-5° should be collected. Yield, 40-45 g.
A brown residue remains in the flask.
Refractionation of the low-boiling impurities gives a further
quantity of the acetoacetate, but if the initial distillation has
been carefully conducted, the amount recovered is less than i g.,
and the refractionation is not worth while. If possible, complete
the preparation in one day. If this is not possible, it is best to
allow the cold crude sodium derivative (before acidification) to
stand overnight, the flask being closed by a cork carrying a cal-
cium chloride tube; the yield will now fall to about 38 g.
Alternatively, the crude ester may be allowed to remain overnight
in contact with the sodium sulphate, but in this case the yield will
fall to about 30 g.
The ethyl acetoacetate obtained as above is sufficiently
pure for most purposes: it should, however, be refractionated
under reduced pressure if a sample of specially high purity is
required.
268 PRACTICAL ORGANIC CHEMISTRY
If a vacuum-distillation apparatus is not available for the above preparation,
the crude product may be distilled at atmospheric pressure and the acetoacetate
collected as the fraction boiling at 175-185°. A pure preparation cannot be
obtained in this way, however, because the ester decomposes slightly when
distilled at atmospheric pressure.
Ethyl acetoacetate is a colourless liquid, d, 1-03, slightly soluble
in water, but almost insoluble in brine. It has a faint but pleasant
odour. It is widely used in chemical syntheses.
Demonstrate both the presence and the interconversion of the keto
and enol forms in the ester thus:
(1) Dissolve about i ml. of the ester in about 3 ml. of ethanol and
then add 2-3 drops of aqueous ferric chloride solution. A deep violet-
red coloration at once appears. This is strong evidence for the presence
of the enol form, since similar colorations with ferric chloride are given
by most phenols (p. 338) and many higher aliphatic hydroxy-com-
pounds. Now pour the solution into about ioo ml. of distilled water
in a beaker and add bromine water drop by drop with vigorous stirring
until the solution just becomes colourless. On standing, the violet-red
ferric chloride coloration soon reappears with increasing intensity.
The bromine has thus added on at the double bond of the enol form,
giving the unstable dibromo derivative (A), which readily loses hydrogen
Br 2 -HBr
CH8C(OH):CHCOOC2H6 —I CH3C(OH)BrCHBrCOOC2H6- ->
(A)
CH3CO-CHBrCOOC2H6
(B)
bromide to give the monobrom-foto ester (B). Since the violet-red
ferric chloride coloration is given only by the enol form, the temporary
removal of the Jatter by the bromine causes the solution to become
momentarily colourless. Some of the unchanged keto form then
changes over to the enol in order to re-establish the original equilibrium,
and the ferric chloride coloration therefore reappears. The process can
be repeated several times by the subsequent addition of bromine. If a
slight excess of bromine water is originally added after the solution
becomes colourless, the slow fading of the yellow bromine solution can
be observed as it reacts with the enol form, then the solution becomes
momentarily colourless, and finally the violet-red coloration reappears
as before.
(2) To 2 ml. of the ester in a test-tube add slightly more than the
same volume of a cold saturated aqueous copper acetate solution.
The blue colour of the latter turns immediately to a pale green. Now
shake the tube vigorously in order to produce an emulsion of the ester
in the aqueous layer. Scratch the sides of the tube with a rod, and
shake vigorously as before. Crystallisation may be delayed for about
5 minutes, but, when once started, rapidly gives a copious precipitate
PREPARATIONS 269
of the pale green cupric derivative (C) of the enol form. If the contents
of the tube are now shaken with chloroform, the crystals of the cupric
compound readily dissolve in the lower chloroform layer, showing
clearly that it is not a normal ionised salt.
CH 3 C: CH • C • OC 2 H 6 CH 3 COCH 2 COOC 2 H 5 + NaHSO3
I Il I
O O +
\ / CH3C(OH).CH2COOC2H6
Cu I
/ \ SO3Na (D)
O O

CH 3 CiCH-C-OC 2 H 5 (C)
(3) To 2 ml. of the ester, add 2-3 drops of a saturated freshly
prepared solution of sodium bisulphite. On shaking, a gelatinous
precipitate of the bisulphite addition product (D) of the keto form
separates, and on standing for 5-10 minutes usually crystallises out.
This is a normal reaction of a ketone (see p. 344): hydrogen cyanide
adds on similarly to give a cyanhydrin.
Note. To obtain satisfactory results with tests (2) and (3), pure re-
distilled ethyl acetoacetate should be used.
For further experimental evidence for the presence of the enol form,
see Tests i, 2 (a) and 2 (b), p. 274.
SYNTHETIC USE OF ETHYL ACETOACETATE. In view of the great importance
of the ester in synthetic work, the following practical points concerning its use
should be borne in mind.
Mono- and Di-substitution Derivatives. The enolic sodium derivative of
ethyl acetoacetate (E) is prepared by mixing ethanolic solutions of the ester
and of sodium ethoxide. It should not be prepared by the direct action
of metallic sodium on the ester, as the reaction is slow and the nascent
hydrogen evolved reduces some of the ester to ethyl (3-hydroxy-butyrate,
CH 3 CH(OH)CH 2 COOEt.
When the sodium derivative, which is used in ethanolic solution without
intermediate isolation, is boiled with an alkyl halide, e.g., methyl iodide,
XaOEt _ MeI
CH 3 COCH 2 COOEt ^CH 3 COCHCOOEt ^CH 3 COCH(Me)COOEt
(E) (F)
N7aOEt EtI
CH 3 COCH(Me)COOEt ^CH 3 C(ONa):C(Me)COOEt *-
(F) (G) CH 3 COC(Me)COOEt
(H)
the methyl derivative (F) of the ketonic form is produced. The latter can
then be treated again with sodium ethoxide (both in ethanolic solution as
before) and the enolic sodium derivative (G) of the methyl compound thus
formed. The latter can then be boiled in solution as before with an alkyl
270 PRACTICAL ORGANIC CHEMISTRY
halide such as ethyl iodide, and the methyl-ethyl compound (H) obtained.
It follows therefore that (i) even with a large excess of sodium ethoxide, a di-
sodium derivative cannot be obtained and therefore a di-substituted derivative
(H) must be prepared through the intermediate formation of the mono-sub-
stituted derivative (F); (2) the substituent groups* must be alkyl groups or
substituted alkyl groups such as benzyl, C 4 H 6 CH 8 -, and that aryl groups
cannot be introduced, because, e.g., iodo-benzene would not react with sodium
derivatives such as (E) or (G). Therefore the synthesis of aryl compounds
has usually to be accomplished by entirely different means, such as by the
Grignard reagent.
Hydrolysis. Ethyl acetoacetate when treated with cold dilute sodium hydrox-
ide solution gives the sodium salt of acetoacetic acid. This acid is unstable, and
readily breaks down into acetone and carbon dioxide: it is of considerable
CH3COCH2COOH = CH3COCH8 -f COt
physiological importance, as it occurs with acetone in diabetic urine, both
compounds being initially formed from p-hydroxy-butyric acid.
The important methods of hydrolysis of acetoacetic ester derivatives are
however:
(1) Ketonic Hydrolysis. Hot dilute caustic alkalis or hydrochloric acid first
hydrolyse off the ethyl group, and then remove carbon dioxide, a mono- or
di-substituted acetone being thus obtained:
CH 3 COCH(Me)CO 2 Et CH 3 COC(Me)(Et)CO 2 Et
I H2O I H2O
CH3COCHMe + CO2 + EtOH CH3COCHMeEt + CO2 + EtOH
(2) Acidic Hydrolysis. Hot concentrated caustic alkalis first hydrolyse off
the ethyl group, and then split the molecule to give one equivalent of acetic acid
and one equivalent of the mono- or di-substituted acetic acid (as their alkali
salts).
CH3CO|CH(Me)COO]Et CH 3 COlC(Me)(Et)COOiEt
OHJH I H JOH OHJH I HiOH
CH8COOH 4- MeCH 2COOH -f EtOH CH3COOH + MeEtCHCOOH + EtOH
In brief, suitable hydrolysis of ethyl acetoacetate derivatives will give mono-
or di-alkyl substituted acetones or acetic acids. Tri-substituted acetones or
acetic acids cannot be obtained: moreover, the di-substituted acetones must

* Acyl halides, both aliphatic and aromatic, react with the sodium deriva-
tive, but the product depends largely on the solvent used. Thus acetyl chloride
reacts with the sodium derivative (E) suspended in ether to give mainly the
C-derivative (i) and in pyridine solution to give chiefly the O-derivative (2).
These isomeric compounds can be readily distinguished, because the C-
denvative ( i ) can still by enolisation act as a weak acid and is therefore
(i) CH8COCHCOOEt (2) CH3CiCHCOOEt
COCH3 OCOCH3
soluble in alkalis, while the O-derivative (2) is neutral and insoluble in alkalis.
PREPARATIONS 271
have the two substituents joined to the same carbon atom, symmetrically
substituted ketones not being obtainable from the ester by the above methods.
For other examples of the synthetic application of ethyl acetoacetate, see
below and pp. 293 295.

Methyl-phenyl-pyrazolone.
The preparation of methyl-phenyl-pyrazolone illustrates one of the synthetic
uses of ethyl acetoacetate, as distinct from those involving the hydrolysis of
substitution derivatives.
If ethyl acetoacetate is warmed with an equivalent quantity of phenyl-
hydrazine, the corresponding phenylhydrazone (A) is readily formed. On
CH 3 CO -r H 2 NNHC 6 U 5 CH 3 CiNNHC 6 H 6
I - H2O - I
CH 2 COOC 2 H 6 CH 2 COOC 2 H 5 (A)
further heating, ring formation occurs with the loss of ethanol and the pro-
CH3CrNNHC6II5 CH 3 C:N NC 6 H 6
I - C 2 H 5 OH -f I I
CH 2 COOC 2 H 5 CH2-CO (B)
duction of methyl-phenyl-pyrazolone (B). To indicate the CH 3 CiN-NC 6 H 6
3 2l
position of the substituents in the pyrazolone ring, the
atoms in this ring are numbered as shown, and the com- 4 5
pound is thus 3-methyl-i-phenyl-5-pyrazolone. CH2-CO
Required: Ethyl acetoacetate, 6-2 ml.; phenylhydrazine, 5 ml.
Mix 6-2 ml. (6-4 g.) of pure ethyl acetoacetate and 5 ml.
of pure phenylhydrazine* in an evaporating-basin of about 75 ml.
capacity, add 0-5 ml. of acetic acid and then heat the mixture on
a briskly boiling water-bath (preferably in a fume-cupboard) for
i hour, occasionally stirring the mixture with a short glass rod.
Then allow the heavy yellow syrup to cool somewhat, add 30-40
ml. of ether, and stir the mixture vigorously; the syrup may now
dissolve and the solution shortly afterwards deposit the crystal-
line pyrazolone, or at lower temperatures the syrup may solidify
directly. (Note. If the laboratory has been "inoculated" by
previous preparations, the syrup may solidify whilst still on
the water-bath: in this case the solid product when cold must
be chipped out of the basin, and ground in a mortar with
the ether.) Now filter the product at the pump, and wash
the solid material thoroughly with ether. Recrystallise the
product from a small quantity of a mixture of equal volumes
of water and ethanol. The methyl-phenyl-pyrazolone is obtained
* The use of impure reactants may give a deep red syrup and delay consider-
ably the final solidification: they should, therefore, be redistilled in a vacuum
before use.
272 PRACTICAL ORGANIC CHEMISTRY
as colourless crystals, m.p. 127°. Yield of recrystallised material,
6-0-6-5 g-
The tautomerism shown by the pyrazolones is of considerable interest.
Thus the above methyl-phenyl-pyrazolone when fused or in solution can exist in
the tautomeric forms (C), (D), and (E).
CH3C : N-NC 6 H 6 CH 3 C-NHNC 6 H 6 CH3CrN-NC9H6
I I ^ Il I ^ I I
CH2-CO (C) CH — CO (D) CH = C(OH) (E)
When the methyl-phenyl-pyrazolone is heated with methyl iodide in methano-
lic solution, it acts in the form (D), the -XH- group undergoing methy-
lation, with the formation of the hydriodide of 2,3-dimethyl-i-phenyl-
5-pyrazolone, or antipyrine (F), a drug used (either as the free base or as the
CH 8 C-N(CHs)-NC 6 H 6 CH 3 C-N(CH,)-NC 6 H 5
Ii I Il I
CH - CO (F) (CH 3 ) 2 N C --- CO (G)
salicylate) to remove pain and also to reduce the body temperature. Anti-
pyrine in turn can be converted to 2,3-dimethyl-4-(dimethylamino)-i-phenyl-5-
pyrazolone, or pyramidon (G), a drug which has physiological properties similar
to those of antipyrine, but which is effective in smaller doses and is more free
from harmful after-effects.

Ethyl Malonate. CH2(COOC2H6)2.


A concentrated solution of monochloroacetic acid is neutralised with sodium
bicarbonate, and then heated with potassium cyanide, whereby sodium cyano-
acetate is obtained:
CH2ClCOONa + KCN = CH 2 (CN)COONa + KCl
The crude product is evaporated to dryness and then heated with a mixture
of ethanol and sulphuric acid: the cyano group is thus hydrolysed giving
malonic acid, which then undergoes esterification to give diethyl malonate.
/COONa „ , . . /COOH _ .- . /COOC 8 H 6
/ Hydrolysis / Estenncation /
CH1 -- > CH8 -> CH 2
\:N
Required: Monochloroacetic acid, 30 g.; sodium bicarbonate,
30 g.; potassium cyanide, 24 g.; sulphuric acid, 50 ml.; rectified
spirit, 70 ml.
The first part of this preparation (as far as the solidification of
the sodium cyanoacetate) must be carried out in the fume-cupboard.
Add 30 g. of monochloroacetic acid to 60 ml. of water con-
tained in a wide evaporating-basin (about 12-15 cm. in diameter)
and warm the mixture gently on a sand-bath until the tempera-
ture reaches about 55°, using a 260° thermometer as a stirrer for
PREPARATIONS 273
this purpose. Now add powdered sodium bicarbonate* (about 30
g.) in small quantities at a time with stirring until the evolution
of carbon dioxide is complete, and the solution is just alkaline to
litmus-paper: during this operation keep the temperature of the
mixture between 5 5°and 6o°. Now remove the basin from the sand-
bath and cautiously add 24 g. of powdered potassium cyanide,!
continuing the stirring both during and after the addition. The
temperature of the mixture rises spontaneously after the addition
is complete and the cyanide rapidly dissolves. When the tem-
perature of the well-stirred mixture reaches 90-95°, a vigorous
effervescence usually occurs for a few seconds and then rapidly
subsides. When this reaction is over, replace the basin on the
sand-bath and heat gently, meanwhile stirring the brown solution
with the thermometer until the temperature reaches 135° (about
30 minutes' heating is usually required). Maintain the tempera-
ture at 135° for a further 5 minutes, and then remove the basin
from the sand-bath and continue stirring until the product
solidifies.
Without undue delay, chip out the brown solid mass (which
is deliquescent when cold) and place the coarsely broken mass
in a 400 ml. round-bottomed flask fitted with a reflux water-
condenser: add 20 ml. of rectified spirit and shake well around
until the product is uniformly wet. Now add 50 ml. (92 g.) of
concentrated sulphuric acid carefully with shaking to 50 ml.
(40 g.) of rectified spirit in a 200 ml. conical flask, keeping the
mixture well cooled in ice-water during the addition. Pour this
solution in small portions down the reflux condenser, shaking
well after each addition. When the addition is complete, heat the
flask on a boiling water-bath for i hour, with occasional shaking.
Then allow it to cool somewhat (the contents will become almost
solid if allowed to become quite cold), add 70 ml. of water down
the condenser, and shake vigorously. Filter any insoluble mater-
ial at the pump, and wash the residue on the filter several times
with a few ml. of ether. Transfer the filtrate (with the ether
washings) to a separating-funnel and extract several times with
ether. Discard the aqueous layer, return the united ethereal
extracts to the funnel, and shake them cautiously with sodium
carbonate solution several times until no further evolution of
carbon dioxide occurs: traces of sulphuric acid and of ethanol
are thus removed. Finally separate the ethereal layer and dry it
over granular calcium chloride in a small conical flask for at least
30 minutes.
* Strictly named by ILTAC nomenclature as sodium hydrogen carbonate,
f Sec footnote, p. 191.
274 PRACTICAL ORGANIC CHEMISTRY
Meanwhile fit up an apparatus for ether distillation precisely
similar to that shown in Fig. 64 (p. 163), except that a ioo ml.
Claisen flask is used instead of the simple distillation-flask shown
in the figure, i.e., as in Fig. 23(E), p. 45. The dropping-funnel is
fitted to the main neck of the Claisen flask, the side-neck being
corked. Filter the dry ethereal solution through a fluted filter-
paper directly into the dropping-funnel, finally washing the
conical flask and the calcium chloride with a few ml. of fresh
ether. Then distil off the ether in the usual way, allowing the
solution to fall from the dropping-funnel into the flask as fast as
the ether itself distils over—observe all the usual precautions for
ether distillations. When the distillation of the ether is complete
and only the crude ester remains in the Claisen flask, fit up the
latter for vacuum-distillation, using the simple apparatus shown
in Fig. i2(A), (p. 29) or a Perkin triangle with condenser (Fig. 14,
p. 31) or the condenser and "pig" shown in Fig. 23(F), p. 46,
and heating the flask in an oil-bath. The ethyl malonate usually
distils as a sharp fraction boiling over a range of about 2-3°: it
may be recognised from the following b.p.s: 93°/i6 mm.,
iO5°/z6 mm. Yield, about 35 g. If necessary the ethyl malonate
may be distilled at atmospheric pressure, at which it has b.p. 198°:
slight decomposition occurs in these circumstances, however, and
the distillate, although colourless, has a slightly acrid odour.
Diethyl malonate is a colourless liquid, d, 1-07; it has a faint
pleasant odour, and is only slightly soluble in water.
Ethyl malonate, like ethyl acetoacetate, exists as a tautomeric
mixture of keto and enol forms, although in the case of ethyl malonate
C 2 H 5 OOC-CH 2 -COOC 2 H 6 ^ C 2 H 5 OOC-CHiC(OH)OC 2 H 6
keto enol
the proportion of enol form present at room temperature is exceedingly
small. Experimental evidence for the presence of the enol form is,
however, given by the following tests:
(1) To 2 ml. of a freshly prepared dilute aqueous solution of sodium
nitroprusside, add 2 drops of ethyl malonate and shake: then add 2-3
drops of io% aqueous sodium hydroxide solution and shake again. A red
coloration at once appears, but fades in a few minutes to pale brown.
(2) (d) Dissolve about o-i g. of pure m-dinttrobenzene in 2-3 ml.
of ethanol, and then add an equal volume of io% aqueous sodium
hydroxide solution. (Ignore traces of the dinitrobenzene that may be
reprecipitated by the soda.) Now add 2 drops of ethyl malonate and
shake. A deep reddish-violet coloration is produced, but rapidly
changes to a deep red.
(b) Dissolve 0-2 g. of 3,5-dinitrobenzoic acid in 2-3 ml. of 10%
PREPARATIONS 275
aqueous sodium hydroxide solution, and then add 2 drops of ethyl
malonate and shake. A violet coloration is produced, rapidly fading to
red and eventually to pale yellow. Excess of the malonate discharges
the red colour rapidly, giving the yellow solution.
Precisely similar results are obtained with ethyl acetoacetate, except
that in tests 2 (a) and 2 (b) the deep red coloration is produced without
a preliminary violet coloration.
These coloration changes are given by most compounds which possess
the -CH 2 -CO- group: for further examples, see Tests 4 (a) and (b)
for Ketones, p. 344.
SUBSTITUTION DERIVATIVES OF ETHYL MALONATE. Ethyl malonate resembles
ethyl acetoacetate in that it gives rise to mono- and di-substituted derivatives
in precisely similar circumstances. Thus when ethanolic solutions of ethyl
malonate and of sodium ethoxide are mixed, the sodium derivative (A) of the
enol form is produced in solution. On boiling this solution with an alkyl
halide, e.g., methyl iodide, the methyl derivative (B) of the keto form is obtained.
When this is treated again in ethanolic solution with sodium ethoxide, the
- MeI NaOEt
EtOOCCHCOOEt ^ EtOOC-CH(Me)COOEt >
(A) (B)
EtI
EtOOCC(Me)COOEt > EtOOC-C(Me)(Et)COOEt
(C) (D)
corresponding sodium derivative (C) is formed: this in turn when boiled in
ethanolic solution with any alky I halide, e.«., ethyl iodide, gives the ethyl-
methyl derivative (D), i.e., the diethyl ester of ethylmethylmalonic acid. In this
way, any mono-substituted (B) or di-substituted (D) alkyl derivative may be
obtained.
Hydrolysis. Ethyl malonate and its derivatives are usually readily hydrolysed
on boiling with aqueous alkalis, the salts of the corresponding dicarboxylic
acids being thus obtained: the course of this hydrolysis is unaffected by the
concentration of the alkali used. The free acids, having two -COOH groups
joined to one carbon atom, are unstable when heated, and immediately above
their melting-points (or sometimes in boiling aqueous solution) lose carbon
dioxide, a monobasic acid being obtained. Thus the mono-substituted ester
(B) on hydrolysis gives mono-methyl-rnalonic acid (E) which on being heated
to its m.p. gives methyl-acetic or propionic aeid (F). The di-substituted ester
(D) similarly gives first ethylmethylmalonic acid (G) and then cthylmethyl-
acetic acid (H).
EtOOC-CH(Me)COOEt > HOOCCH(Me)COOH >
(B) (E) CH 2 (Me)COOH + CO3
(F)
EtOOC-C(Me)(Et)COOEt + HOOCC(Mc)(Et)COOU >
(D) (G) CH(Me)(Et)COOH + CO,
(H)
276 PRACTICAL ORGANIC CHEMISTRY
It follows therefore that ethyl malonate can be used (just as ethyl aceto-
acetate) to prepare any mono- or di-substituted acetic acid: the limitations are
identical, namely the substituents must necessarily be alkyl groups (or aryl-
alkyl groups such as C 6 H 6 CH 2 ), and tri-substituted acetic acids cannot be
prepared. Ethyl malonate undergoes no reaction equivalent to the ketonic
hydrolysis of ethyl acetoacetate, and the concentration of the alkali used for the
hydrolysis is therefore not important.

Ethane Tetracarboxylic Ethyl Ester.


(C 2 H 5 OOC) 2 CH-CH(COOC 2 H 5 ) 2 .
When an ethanolic solution of the sodium derivative of ethyl malonate is
shaken with a solution of iodine, the latter withdraws the sodium, and the
ethyl malonate residues link together in pairs to give the tetra-ethyl ester of

XaCH(COOC 2 HJ 2 CH(COOC 2 H 6 ) 2
2NaI
I, r ""'"I +
NaCH(COOC 2 H-,), CH(COOC 2 H 6 ) 2
syw-ethane tetracarboxylic acid.
Required: Ethanol, 30 ml.; sodium, 1-4 g.; iodine, 7-7 g.; ethyl
malonate, 9 ml.; sodium thiosulphate solution.
Place 30 ml. of ethanol in a 200 ml. conical flask fitted to a
reflux water-condenser, and then add 1-4 g. of sodium cut into
small pieces. The sodium rapidly dissolves to give a solution of
sodium ethoxide, the ethanol boiling under the heat of the
reaction. When the sodium has completely dissolved, detach
the flask and cool it in ice-water.
While the sodium ethoxide solution is cooling, prepare a solu-
tion of 7-7 g. of finely powdered iodine in 60 ml. of ether. When
this solution is ready, add 9 ml. (9-6 g.) of ethyl malonate to the
ethanolic sodium ethoxide solution, mix well and then allow to
stand for 30-60 seconds (not longer}: then cautiously add the
ethereal solution of the iodine, mixing thoroughly during the
addition in order to avoid local overheating by the heat of the re-
action. (If, after the ethyl malonate has been added to the
sodium ethoxide, a considerable delay occurs before the iodine is
added, the yield of the final product is markedly decreased.)
Now cork the flask securely, and shake it vigorously for about
5 minutes: the solution should now have only a faint brown
colour due to unchanged iodine. Cool the mixture in ice-water,
pour it into a separating-funnel, and extract it twice with water to
remove sodium iodide and most of the ethanol. Then shake the
residual ethereal solution with a dilute aqueous solution of sodium
thiosulphate: the excess of iodine is thus removed and the
PREPARATIONS 277
ethereal solution becomes colourless. Separate the ether, dry it
over calcium chloride for about 20 minutes, and then filter it
through a fluted filter-paper directly into a ioo ml. conical flask.
Fit the latter with a delivery knee-tube and water-condenser, and
then, observing all the usual precautions (p. 163), distil off the
ether on a water-bath until about 10-15 m^ remain. Pour this
solution whilst still hot into a small evaporating basin and swirl it
gently around: the hot ether rapidly evaporates and the ethane
tetracarboxylic ester crystallises out. Allow it to stand exposed to
the air for about 10-15 minutes, and then well press the crystals
between several layers of thick drying-paper to remove any liquid
residue. Recrystallise from a small quantity of rectified spirit or
of light petroleum (b.p. 60-80°). The ester is obtained as colour-
less crystals, m.p. 76°: yield, 6*o-6'5 g.
This tetra-ethyl ester is difficult to hydrolyse: the corresponding tetra-
methyl ester can, however, be hydrolysed to give ethane tetracarboxylic acid,
(HOOC) 2 CH-CH(COOH) 2 . The latter readily loses 2 molecules of carbon
dioxide (on being heated or even on boiling with water) to give succinic acid,
HOOC-CH 2 -CH 2 COOH.
Ethane tetracarboxylic ethyl ester can be regarded as composed of two
malonic ester residues, each acting as a mono-alkyl substituent to the other.
The two remaining hydrogen atoms therefore still retain acidic properties, and
consequently the ester gives with sodium ethoxide a di-sodium derivative,
NaC(COOEt) 2 C(COOEt) 2
I + I2 = I + 2NaI
NaC(COOEt)8 C(COOEt) 2
which when treated with iodine gives in turn ethylene tetracarboxvlic ethyl
ester, m.p. 57°.

5,5-Dimethyl-cyclohexan-i,3-dione. (Dimedone.)
(The Michael Reaction.)
The Michael Addition Reaction consists in the addition of the sodio-derivative
of ethyl acetoacetate, ethyl malonate or ethyl cyanoacetate to an olefine group

MeC CH-C-CH 3 + Me 2 C-CI-T-C-CH 3 ^Me 2 C-CH 2 -CO-CH 3


(I) Na CH(COOEt) 2 ( I I ) CH(COOEt) 2 Na ( I I I ) CH(COOEt) 2

CH 2 -CO CH,- CO
-^ Me 2 C< )CH 2 __> Me 2 C< " JXH 2
CH-CO CH 2 -CO
( I V ) COOEt (V)
278 PRACTICAL ORGANIC CHEMISTRY
which is activated by (in particular) a keto, nitrile or ester (-COOR) group. Thus
the addition of diethyl sodio-malonate to mesityl oxide (I) may be regarded
essentially as an ionic addition to give the anion (II), which on acidification gives
the ester (III) with the keto group regenerated. The Michael Reaction has
clearly a wide scope in synthetic work.
The compound (III) can however lose ethanoi by an internal Claisen ester
condensation (p. 264) to give the cyclohexane derivative (IV), which, being the
ester of a (3-keto acid, in turn readily undergoes hydrolysis and decarboxylation
to give 5,5-dimethyl-cyclohexan-i,3-dione (V) or "Dimedone," a valuable
reagent for the detection and estimation of formaldehyde.

Required: Ethanoi, 40 ml.; sodium, 2-3 g.; ethyl malonate,


17 g.; mesityl oxide, 10-2 g.; sodium hydroxide, 10 g.
The mesityl oxide (b.p. 130°) and the ethyl malonate (b.p. 199°,
95°/18 mm.) should be redistilled before use.
Assemble a 250 ml. three-necked flask, fitted with a stirrer, a
reflux condenser and a dropping-funnel, as in Fig. 22(A) and (j),
p. 43, or Fig. 23(0), p. 46 (or a two-necked flask, with the funnel
fitted by a grooved cork (p. 255) to the top of the condenser).
Place 40 ml. of ethanoi in the flask, and then add 2-3 g. of
sodium cut into small pieces. When all the sodium has dis-
solved, heat the stirred solution on the water-bath,* and run
in from the funnel 17 g. (17 ml.) of ethyl malonate and then
(more slowly) 10-2 g. (12 ml.) of mesityl oxide, the reaction-
mixture meanwhile forming a thick slurry. Boil the stirred
mixture under reflux for i hour, and then add a solution of 10 g.
of sodium hydroxide in 50 ml. of water, and continue boiling
the pale honey-coloured solution for i£ hours more.
Whilst the solution is still hot, add dilute hydrochloric acid
until the stirred solution is just acid to litmus, and then distil
off as much ethanoi as possible, using the water-bath. Now add
more dilute hydrochloric acid to the residual hot solution until
it is just acid to methyl-orange. The 5,5-dimethyl-cyclohexan-
i,3-dione separates as an oil which solidifies on cooling. Filter
the product at the pump, wash it with ice-cold water, and dry
it in a desiccator. Yield of the pale cream-coloured crystals,
12 g.; m.p. 136-145° (preliminary softening).
Recrystallisation from a mixture of equal volumes of petroleum
(b.p. 60-80°) and acetone gives colourless crystals, m.p. 146-
148°.
Reactions. The methylene group in the 2 position in 5,5-
dimethyl-cyclohexan-i,3-dione (V) is strongly activated by the
* The whole apparatus can conveniently be assembled on the water-bath,
which is heated as the last pieces of sodium are reacting.
PREPARATIONS 279
two adjacent carbonyl groups. The reactivity is shown by the
following reactions:
(i) If a warm aqueous solution is treated with aqueous sodium
hypoiodite solution, a reaction analogous to the iodoform
reaction occurs, with the formation of p p-dimethylglutaric acid

CH 2 CO
Me2C< )CH 2 + NaIO -»- Me 2 C(CH 2 COONa) 2 H-CHI,
CH 5 CO

and iodoform.
(2) The "Dimedone" (V) in ethanolic solution reacts rapidly
with formaldehyde to give "methylene-dimedone" (VI) which,

CH2-CO CH2-CO /COCH 2


2Me2C<; >CH 2 + HCHO -*- Me2C( )CH CH2-C^ )
CH2-CO CH2-(^O Vo-
(VI)

having a low solubility, readily crystallises out, and has a sharp


m.p. (c/. p. 146). Many aldehydes can be identified by their
analogous "alkylidene-dimedone" derivatives, which also serve
to distinguish aldehydes from ketones.

Sorbic Acid. CH3-(CH:CH-)2COOH. (The Knoevenagel


Condensation.)
The term Knoevenagel Condensation was originally applied to the base-
catalysed condensation of the carbonyl (:CO) group of aldehydes and ketones
with the reactive methylene group of malonic acid, with loss of water:
RCHO + H1C(COOH)2 -» R-CH:CH-COOH + H8O + CO2
It is now applied more widely to include malonic acid derivatives, such as
diethyl monoethyl-malonate, ethyl cyanacetate, etc. Various amines may be
used as catalysts, and usually the most effective is piperidine (hexahydro-
pyridine): a mixture of piperidine and pyridine, or pyridine alone, is also often
used.
The role of the base is apparently primarily that of a proton remover from
the reactive methylene group: thus if B represents the base, reaction (i) gives
the carbanion, which then combines with the positive carbon of the carbonyl
group (reaction ii): the product regains a proton from the piperidinium ion,
and then by loss of water followed by mono-decarboxvlation of the malonic
acid residue gives the final acid.
28o PRACTICAL ORGANIC CHEMISTRY

(i) CH2(COOH)1 + 38 -» £H(COOH,B)a + BH

O H
(ii) R-C=O f -CH(COOH^B) 2 -^- R-C-C(COOH,B)2
H H
H
O H
-^ R C-C(COOH,B) 2 + R-CHrC(COOH) 2 -V R CH:CH COOH
H

The reaction is readily illustrated by the formation of crystalline sorbic acid


by the condensation of crotonaldehyde and malonic acid in hot pyridine
solution:
CH 3 -CHiCH-CHO + H2C(COOH)2 -* CHS-CH:CH-CH:CH-COOH
+ H8O + CO1
Required: Malonic acid, 4 g.; pyridine, 4 ml. (4 g.); croton-
aldehyde, 3-1 ml. (2-7 g.).
Add 4 g. of malonic acid to 4 ml. of pyridine, and then add
3-1 ml. of crotonaldehyde. Boil the mixture gently under reflux
over an asbestos-covered gauze, using a small Bunsen flame, for
40 minutes and then cool it in ice-water. Meanwhile add 2 ml.
of concentrated sulphuric acid carefully with shaking to 4 ml. of
water, cool the diluted acid, and add it with shaking to the
chilled reaction-mixture. Sorbic acid readily crystallises from
the solution. Filter the sorbic acid at the pump, wash it with a
small quantity of cold water and then recrystallise it from water
(ca. 25 ml.). The colourless crystals, m.p. 132-133°, weigh
i-o-i-2g.
Sorbic acid could theoretically, by virtue of the two olefine linkages,
exist in four geometrically-isomeric forms. The above synthesis gives
only one form, which is undoubtedly the trans-trans form, analogous
to the aoi-diphenylpolyenes (p. 238) which are also normally produced
solely in one form.

The Grignard Reagent.


Grignard reagents are prepared by the interaction of alkyl or aryl
halides (of general formula RX) with magnesium in the presence of
ether, or (much more rarely) certain other solvents. Although the
ether certainly takes part both in the formation and the composition of
the Grignard reagent, the formation of the latter can, for the purpose of
interpreting its reactions, be represented as a simple addition:
RX + Mg = RMgX.
PREPARATIONS 281
For the preparation of the Grignard reagent, the following factors
should be noted:
(1) Alkyl and aryl iodides usually react with magnesium more rapidly
than the corresponding bromides, and the bromides very much more
rapidly than the chlorides. Aryl (as distinct from alkyl) chlorides
have usually only a slow reaction with magnesium and are there-
fore very rarely used. With alkyl and aryl iodides in particular,
however, a side reaction often occurs with the formation of a hydro-
carbon and magnesium iodide:
2RI + Mg= R - R + MgI 2
Hence as a general rule the bromides are used.
(2) The formation of the Grignard reagent is inhibited by traces of
water, which also decompose the reagent when it is formed. Therefore
the apparatus used must be thoroughly dry, and the ether anhydrous
(p. 82). Specially prepared magnesium turnings* should preferably
be used: if magnesium ribbon is employed, it should first be drawn
through two layers of fine emery paper to remove the superficial film
of oxide, etc.
(3) In spite of these precautions, it is sometimes found difficult
to start the formation of the reagent, although when once the forma-
tion has started, it proceeds with increasing speed. In such cases it is
advisable to add a small crystal of iodine, which is allowed to fall
through the ethereal solution of the organic halide on to the surface of
the magnesium below. If the mixture is undisturbed, a local concen-
tration of iodine in solution is thus obtained in immediate contact with
the magnesium: the latter then usually becomes reactive, and the
formation of the Grignard reagent, starting in the immediate neighbour-
hood of the iodine, rapidly spreads throughout the magnesium turnings.
Alternatively, a trace of methyl iodide can be added to the ether to
stimulate the reaction with the magnesium, although the resulting
Grignard solution will then contain minute quantities of methyl
magnesium iodide.
No attempt is made to isolate the Grignard reagent from its ethereal
solution before use. The reagent (usually also in ethereal solution) is
added to the solution of the Grignard reagent, and when the reaction is
complete the product is hydrolysed.
The method of hydrolysis depends on the nature of the product.
It is usually sufficient to add dilute sulphuric acid to the ethereal
solution and to shake thoroughly, when the magnesium enters the
aqueous solution, whilst the organic compound remains in the ether.
Alternatively, however, the ethereal solution may be poured on to
ice and water, and then treated with dilute sulphuric acid. Should
the product be affected by this acid, the hydrolysis can be carried out
with an aqueous solution of ammonium chloride. In the following ex-
amples the hydrolysis is usually shown as a simple double decomposition
• Supplied for this purpose by chemical dealers.
282 PRACTICAL ORGANIC CHEMISTRY
with water, giving magnesium hydroxy-iodide: it will be understood that
the latter dissolves in the dilute acid to give a mixture of magnesium
iodide and sulphate.
SYNTHETIC USE OF GRIGNARD REAGENTS. Grignard reagents can be used
to synthesise a wide variety of organic compounds, and are consequently of
very great value in organic chemistry: the chief reactions are summarised
in the following table, in which magnesium methyl iodide (denoted as MeMgI,
in order to differentiate the methyl group introduced by the reagent from any
methyl groups already present in the organic compound) is used as a typical
Grignard reagent.
(1) Water, alcohols and hydroxy compounds generally, and also primary and
secondary amines, give the hydrocarbon corresponding to the Grignard reagent,

MeMgI r HOM - MeH \- Mg (OH)I

MeMgI -f EtOH --> IMeH -f- IVIg(OEt)I

MeMgI + EtXHH - MeH -J- Mg(NHEt)I


(2) Oxygen is directly absorbed, and the product on hydrolysis gives the
corresponding alcohol.
MeMgI °> MeOMgI AIcOMgI -f HOH — MeOH - Mg(OH)I
(3) Carbon dioxide is similarly absorbed, and gives the corresponding
car boxy lie acid.
MeMgI E^! MeCOOMgI
MeCOOMgI -f HOH - MeCOOH T Mg(OH)I

(4) Aldehydes form addition products at the double bond of the carbonyl
(>C:O) group, and hydrolysis gives secondary alcohols. Thus acetaldehyde
gives isopropyl alcohol:
H H
/ /
CH CiO + MeMgI = CH C-OMgI
3 3

/H
ClI3C-OMgI HOH -CH 3 C-OH M K (OH)1

Note. Formaldehyde is a special case. It reacts similarly, but a primary


alcohol is necessarily produced. This alcohol, however, will always contain
one carbon atom more than that obtained in Reaction (2).

/H
HC:O + MeMgI = HC-OMgI
/H
\VIe
PREPARATIONS 283
/H
HC-OMgI + HO H = MeCH 2 OH -f Mg(OH)I
\N , , Ethanol
Me
This reaction is of great value for ascending the homologous series of alcohols:
ROH -* RBr -> RMgBr -> RCH 2 OH
Note that ethylene oxide reacts with the Grignard reagent to give a 2-substi-
tuted ethanol: e.g. with methyl magnesium iodide:
Me-CH 2 CH 2 OMgI -+ Me-CH 2 CH 2 OH
(5) Ketones similarly give tertiary alcohols.
CH 3 CH 3 /OMgI
>C:O -f MeMgI - )C(
7 7 X
CH 3 CH 3 Me
Acetone
CH 3x /OMd HOH CH 3 x X)H
yC/ _, )C( -t Mg(OH)I.
X
CH 3 / \VIe CH 3 / Me
Tertiary butanol
Note.—Grignard reagents readily act as dehydrating agents by virtue of
Reaction (i). Since aliphatic tertiary alcohols usually readily lose water, an
excess of the Grignard reagent may take the above reaction one stage further
to give an unsaturated hydrocarbon.
CH 3 , /OH CH 2 ^
yC/ -H 2 O = ^C-Me
CH 3 / \Me CH 3 7
(6) Esters (a) and acid chlorides (b) readily react with Grignard reagents to
give ketones, which immediately react with a second equivalent of the reagent
as in (5) to give tertiary alcohols as before.
, OKt IMgMc ,Me
(a) CH 3 C:O --- CH 3 C:O + Mg(OEt)I
Ethyl acetate
, Cl IMgMc ,Me
(6) CH,C:O -> CH 3 C:O 4- MgClI*
Acetyl chloride
(7) Nitriles also react with Grignard reagents to give ketones, which arise
from the hydrolysing action of the dilute sulphuric acid on the intermediate
addition product. Acid amides behave similarly.
CH 3 -C:X+MeMgI -* CH 3 -CiNMgI -> CH 3 -CO-fNH 3
/ /
Me Me

* i.e., equimolecular quantities of magnesium chloride and iodide.


284 PRACTICAL ORGANIC CHEMISTRY
CH 8 -CO NH 2 + 2MeMgI -* CH 5 -C-OMgI -» GH 8
/\ 1
Me NH-MgI Me
(8) Non-metallic halides and covalent metallic ha)ides give their organic
derivatives.
AsCl 3 - 3IMgMe • • • AsMc 3
SnCl 4 - 4IMgMc - SnMc 4 ^ 4
HgCl 2 • 2IMgMe - HgMe 2 - r zMgCH

Since Grignard reagents can easily be obtained from aryl halides, they are of
special value in the synthesis of many aromatic compounds, particularly as,
for reasons already stated (pp. 270, 276), aromatic compounds cannot generally
be prepared by means of ethyl acetoacetate and ethyl malonate.

Triphenyl-carbinol, (C6H5)3COH, from Ethyl Benzoate


and Phenyl Magnesium Bromide. (Grignard Re-
action 6 (a).)
Required: Bromobenzene, 10-5 ml,; dry ether, 75 ml.; granu-
lated magnesium, 2-5 g.; dry ethyl benzoate, 5 ml. (5-29 g.).
Fit a 250 ml. round-bottomed flask to a reflux water-condenser
(each being thoroughly dry) and close the top of the condenser
with a calcium chloride tube. Dissolve 10-5 ml. (15-7 g.) of
dry bromobenzene in 50 ml. of anhydrous ether (preparation,
p. 82), and add about half this solution to 2-5 g. of granulated
magnesium contained in the round-bottomed flask, meanwhile
keeping the rest of the ethereal solution in a small, well-corked
conical flask. Now, since the formation of phenyl magnesium
bromide seldom begins spontaneously, add a crystal of iodine
carefully to the magnesium mixture so that it rests on top of the
metal and there slowly dissolves. If the mixture is allowed to
stand quietly, the formation of the Grignard reagent will probably
start in the neighbourhood of the iodine within a few minutes
(being accompanied by a cloudiness and complete disappearance
of the iodine), and will then continue with increasing vigour until
the ether is boiling. (If this does not happen, warm the mixture
acrefully (without shaking) on the water-bath and then, when the
cation begins, turn out the gas.) When the boiling of the ether
begins to cease, pour about 10 ml. of the remainder of the ethereal
solution of the bromobenzene down the reflux condenser, at once
replacing the calcium chloride tube. Continue in this way until
all the bromobenzene has been added, the solution in the flask
boiling steadily meanwhile. If the bromobenzene solution is
PREPARATIONS 285
added too rapidly, check excessive boiling of the ether by immers-
ing the flask in cold water for a few minutes, taking care, however,
not to stop the reaction entirely.
When the addition of the bromobenzene is complete and the
ether is boiling gently, reheat the flask on the water-bath for a
further 15 minutes to ensure completion of the reaction: the
solution will now be slightly dark in colour, and only a trace of
metallic magnesium should remain.
Now remove the flask from the water-bath, and slowly add a
solution of 5 ml. (5-2 g.) of dry ethyl benzoate in 15 ml. of
anhydrous ether down the condenser in small quantities at a time,
mixing the contents of the flask thoroughly between each addition.
When the boiling of the ether again subsides, return the flask to
the water-bath and reheat for a further 15 minutes. Then cool
the mixture in ice-water, and carefully pour off the ethereal solu-
tion into a mixture of about 60 ml. of dilute sulphuric acid and
ioo g. of crushed ice contained in a flask of about 500 ml.
capacity fitted for steam-distillation, taking care to leave behind
any unchanged magnesium.
Fit securely to the lower end of the condenser (as a receiver) a
Buchner flask, the side-tube carrying a piece of rubber tubing
which falls well below the level of the bench. Steam-distil the
ethereal mixture for about 30 minutes: discard the distillate,
which contains the ether, possibly a trace of unchanged ethyl
benzoate, and also any biphenyl, C 6 H 5 ^C 6 H 5 , which has been
formed. The residue in the flask contains the triphenyl-carbinol,
which solidifies when the liquid is cooled. Filter this residual
product at the pump, wash the triphenyl-carbinol thoroughly
with water, drain, and then dry by pressing between several
layers of thick drying-paper. Yield of crude dry product, 8 g.
The triphenyl-carbinol can be recrystallised from methylated
spirit (yield, 6 g.), or, if quite dry, from benzene, and so ob-
tained as colourless crystals, m.p. 162°.
Triphenyl-carbinol (Semi-micro Scale).
Required: Bromobenzene, 1-05 ml.; dry ether, 7-5 ml.; granulated
magnesium, 0-25 g.; ethyl benzoate, 0-5 ml.
First read the details of the macro-scale preparation above.
Fit a 50 ml. round-bottomed flask to a reflux water-condenser fitted
with a calcium chloride tube. Dissolve 1-05 ml. of dry bromobenzene
in 5 ml. of dry ether and add this solution to 0-25 g. of magnesium
contained in the round-bottomed flask. Now add a crystal of iodine
so that it rests on the magnesium. Warm if necessary to start the
reaction: if the latter becomes too vigorous immerse the flask in cold
286 PRACTICAL ORGANIC CHEMISTRY
water, but do not stop the reaction. Now gently boil the mixture on a
water-bath for 15 minutes to complete the reaction, then remove the
flask from the water-bath and add slowly a solution of 0-5 ml. of dry
ethyl benzoate in 1-5 ml. of dry ether down the condenser. When the
boiling of the ether subsides, continue heating on the water-bath for
15 minutes.
Cool the Mask in ice-water and pour the ethereal solution into a mixture
of about 6 ml. of dil. H 2 SO 4 and io g. of crushed ice contained in
a 50 ml. flask fitted for steam-distillation, taking care to leave behind
any unchanged magnesium. Fit to the lower end of the condenser
a small Buchner flask or boiling-tube with side-arm (45°) carrying a
piece of rubber tubing which falls well below the level of the bench.
Steam-distil the ethereal solution and discard the distillate. The
residue in the flask is triphenyl-carbinol and solidifies on cooling.
Filter at the pump, wash with water, drain and dry. Yield of crude
product 0-6 g. Recrystallise when dry from benzene to obtain colourless
crystals: m.p. 162°.

Ethyl p-Phenyl-p-hydroxy-propionate.
C6H5CH(OH)CH2COOEt. (Reformatsky Reaction.)
The Reformatsky Reaction consists of the interaction of an ester of an oc-
halogeno-acid with an aldehyde, a ketone or another ester in the presence of
zinc. For example, if a mixture of ethyl bromoacetate and benzaldehyde is
heated with zinc, the latter undoubtedly first combines with the ethyl bromo-
acetate to form a Grignard-like reagent (reaction A), which then adds on to
the benzaldehyde just as a Grignard reagent would do (reaction B). The com-
plex so formed, on acidification gives ethyl p-phenyl-p-hydroxy-propionate
(reaction C). Note that reaction A could not satisfactorily be carried out using
BrCH 2 COOC 2 H 6 + Zn > BrZnCH 2 COOC 2 H 5 (A)
H
C 6 H 5 CHO + BrZnCH 2 COOC 2 H 6
/
> C H C-OZnBr (B)
6 6

^CH 2 COOC 2 H 5

C 6 H 5 C-OZnBr dilute acid CflH6CH(OH)C H 2CO OC 2 H 6 (C)


^ CH 2 COOC 2 H,
magnesium instead of zinc, because the magnesium Grignard reagent as fast as
it was formed would react with the ester grouping (p. 283). The Reformatsky
reaction is therefore of great value for the preparation of (3-hydroxy acids, and
also for the preparation of a(3-unsaturated acids, to which the [i-hydrOxy acids
can often be readily converted by dehydration.
Note also that if another ester, of general formula R-COOC 8 H 6 , were used in
place of benzaldehyde in the above reaction, a similar complex would be formed,
and on acidification would give an unstable (3-hydroxy-p-ethoxy ester, which
would very readily lose ethanol with the formation of a 3-keto-ester.
PREPARATIONS 287
O ,OZnBr ,OH
R-C-OC1H6 > R C-CH8COOC1H6 > R-C-CH2COOC,HS
XDC1H5 \3C2H5
> R CO CH2COOC8H5
Required: Zinc powder, 20 g.; ethyl bromoacetate,* 28 ml.;
benzaldehyde, 32 ml.
PREPARATION OF REAGENTS.f It is essential for this preparation
that the zinc powder should be in an active condition. For this
purpose, it is usually sufficient if a sample of ordinary technical
zinc powder is vigorously shaken in a flask with pure ether, and
then filtered off at the pump, washed once with ether, quickly
drained and without delay transferred to a vacuum desiccator. If,
however, an impure sample of zinc dust fails to respond to this
treatment, it should be vigorously stirred in a beaker with 5 %
aqueous sodium hydroxide solution until an effervescence of
hydrogen occurs, and then filtered at the pump, washed
thoroughly with distilled water, and then rapidly with ethanol and
ether, and dried as before in a vacuum desiccator. The ethyl
bromoacetate (b.p. 159°) and the benzaldehyde (b.p. 179°) should
be dried and distilled before use.
A 1500 ml. flask is fitted (preferably by means of a three-necked
adaptor) with a rubber-sleeved or mercury-sealed stirrer (Fig. 20,
p. 39), a reflux water-condenser, and a dropping-funnel (cf.
Fig. 23(0), p. 45, in which only a two-necked adaptor is shown:
or Fig. 23(0)). The dried zinc powder (20 g.) is placed in the
flask, and a solution of 28 ml. of ethyl bromoacetate and 32 ml. of
benzaldehyde in 40 ml. of dry benzene containing 5 ml. of
dry ether is placed in the dropping-funnel. Approximately
io ml. of this solution is run on to the zinc powder, and the
mixture allowed to remain unstirred until (usually within a few
minutes) a vigorous reaction occurs. (If no reaction occurs,
warm the mixture on the water-bath until the reaction starts.)
The stirrer is now started, and the rest of the solution allowed to
run in drop-wise over a period of about 30 minutes so that the
initial reaction is steadily maintained. The flask is then heated
on a water-bath for 30 minutes with continuous stirring, and is
then cooled in an ice-water bath. The well-stirred product is then
hydrolysed by the addition of 120 ml. of 10% sulphuric acid.
The mixture is transferred to a separating-funnel, the lower
aqueous layer discarded, and the upper benzene layer then
* Ethyl bromoacetate is lachrymatory, and the preparation should therefore
be carried out in a fume-cupboard.
fThe reactive dry zinc "wool" can be used without the described treatment.
288 PRACTICAL ORGANIC CHEMISTRY
extracted twice with 20 ml. of 10% sulphuric acid, then with
20 ml. of io% sodium carbonate solution, twice again with the
dilute sulphuric acid, and finally twice with 20 ml. of distilled
water. The benzene solution is then separated and dried over
anhydrous magnesium sulphate or (more slowly) over sodium
sulphate.
A 75 ml. Claisen flask is fitted with a small dropping-funnel in
the main neck, and the filtered benzene solution then run into
the flask from the funnel at approximately the rate at which the
benzene is being distilled off by heating the flask in an oil-bath.
When the solvent has thus been removed, the residue is allowed
to cool whilst the funnel is replaced by the usual capillary tube,
and the distillation is then continued at low pressure obtained by
an efficient water-pump. The ester is obtained as a colourless
liquid, b.p. i45-i55°/i5 mm.: yield, 27-30 g. A second dis-
tillation gives a product of sharper boiling-point. If during the
distillation the ester tends to decompose with foaming, it indi-
cates that the above washing has not been sufficiently thorough:
the application of a lower pressure (e.g., ca. 5 mm. by means of an
oil-pump) will usually give smooth distillation without decompo-
sition. The ester has b.p. i28-i3o°/5 mm.

Ethyl-benzene. C 6 H 5 -C 2 H 5 . (The Fittig Reaction.)


Two methods may conveniently be used to ascend the homologous series of
aromatic hydrocarbons:
(1) The Friedel-Crafts Reaction, in which an aromatic hydrocarbon reacts
with an alkyl halide under the influence of aluminium chloride:
C 6 H 5 H + BrC 2 H 5 -> C 6 H 5 -C 2 H 5 -f H-Br
The preparation of acetophenone (p. 255) is a modification of this method, the
alkyl halide being replaced by an acid chloride, with the consequent formation
of a ketone.
(2) The Fittig Reaction, in which sodium reacts with a mixture of an aryl
and an alkyl halide, forming the sodium halide and the corresponding hydro-
carbon:
C 6 H 5 Br + 2Na + BrC 2 H 5 -> C 6 H 5 -C 2 H 5 -f 2NaBr
This reaction is precisely parallel to the Wurtz Reaction in the aliphatic series,
by which, for instance, w-butane can be obtained by the action of sodium on
ethyl bromide.
2C 2 H 6 Br + 2Na = C 1 H 5 -C 2 H 6 + zNaBr
The Fittig Reaction is employed in the following preparation of ethyl-
benzene.
PREPARATIONS 289
[NOTE. Hydrocarbons such as ethyl-benzene can also be prepared by the
Clemmensen reduction of the corresponding ketone. This is exemplified by the
reduction of />-methylacetophenone (p. 290)].
Required: Sodium, 22-5 g.; dry ether, ioo ml.; bromoben-
zene, 34 ml.; ethyl bromide, 31 ml.
Using the sodium press described on p. 82, press 22-5 g. of
sodium into wire, and allow the latter to fall directly into ioo
ml. of anhydrous ether (preparation, p. 82) contained in a 750
ml. round-bottomed flask. Fit the latter with an efficient
(preferably double-surface) reflux water-condenser, and stand the
flask on a cork ring. Now pour down the condenser a mixture of
34 ml. (50 g.) of dry bromobenzene and 31 ml. (45-5 g.,
i.e., a 30% excess) of ethyl bromide. Close the top of the
condenser with a calcium chloride tube and shake the mixture
thoroughly. After 10-15 minutes, the reaction will cause the
ether to boil steadily. Shake the mixture occasionally during the
next two hours in order to prevent the wire from becoming coated
with sodium bromide, but do not cool the flask unless the boiling
of the ether becomes very vigorous: ultimately a bluish-grey
sludge forms in the mixture, in addition to unchanged wire.
Allow the mixture to stand in this way for a total period of at least
3 hours, and preferably overnight—in the latter case ensure that
the condenser-water is turned off during the night.
Now assemble the apparatus for ether distillation shown in
Fig. 64, p. 163, except that, in place of the small distilling-flask
A, use a wide-necked ioo ml. bolt-head flask, closed by a cork
carrying the dropping-funnel B and also a bent delivery-tube (or
"knee-tube") for connection to the condenser C. (Alternatively,
use the apparatus shown in Fig. 23(E), p. 45.) Carefully decant
the ethereal solution of the ethyl-benzene into the dropping-
funnel B (Fig. 64), leaving as much solid material behind in the
750 ml. flask as possible: wash this solid residue with a further
quantity of ether, decanting the latter in turn into the dropping-
funnel. (The residue in the flask may still contain some un-
changed sodium: therefore place some methylated spirit in the
flask, and then, when all effervescence has subsided, dilute carefully
with water, and finally pour into the sink.) Now distil the ether,
running the ethereal solution into the bolt-head flask as fast as the
ether itself distils over, and observing all the usual precautions
for ether-distillations (p. 163). When no more ether distils over,
detach the bolt-head flask, and fit to it a short fractionating
column, similar to that shown in Fig. n(B), p. 26, a water-con-
denser being then connected in turn to the column. Carefully
290 PRACTICAL ORGANIC CHEMISTRY
fractionate the crude ethyl-benzene, collecting the fraction of b.p.
130-135°. Yield, 16 g.
Ethyl-benzene is a colourless liquid of b.p. 134°, and d, 0-876:
it has only a faint odour.
/7-Ethyltoluene. C 2 H 5 -C 6 H 1 -CH 3 . (Clemmensen Reduc-
tion.)
Many aldehydes and ketones can be reduced directly by Clemmensen's
method, in which the aldehyde or ketone is boiled with dilute hydrochloric acid
and amalgamated zinc. p-Methylacetophenone (or methyl />-tolyl ketone) is
reduced under these conditions to />-ethyltoluene. An excess of the reducing
agent is employed in order to prevent the formation of unsaturated hydrocarbons.
The />-methylacetophenone is readily prepared by the Friedel-Crafts'
reaction (cf. p. 254), toluene being treated with acetyl chloride in the presence of
aluminium chloride. The toluene is employed in considerable excess so that it

CH3 \ T > + ClCOCH 3 > CH 8 \_>


\? COCH 3 + HCl
may act both as a reagent and a solvent. Note that in this reaction ortho-
substitution is negligible, and the pure ^-methylacetophenone is obtained.
p-METHYLACETOPHENONE. Required: Toluene, 250
ml.; acetyl chloride, 35 ml.; aluminium chloride, 40 g.
This preparation should be carried out in a fume-cupboard.
Fit a 500 ml. flask (preferably by means of a three-necked adaptor)
with a stirrer having a rubber-sleeved or mercury seal, a dropping-
funnel and, by means of the third outlet, with a calcium chloride tube.
Place 250 ml. of dry toluene and 40 g. of aluminium chloride in the
flask, and cool the latter in an ice-water bath inside a fume-cupboard.
(Ensure that the aluminium chloride is a fresh sample, i.e., that it has
not been long stored in a previously opened bottle, and pulverise it if
necessary immediately before use.) When the mixture has been
thoroughly cooled, place 35 ml. of acetyl chloride in the dropping-
funnel, and allow it to run drop-wise into the flask over a period of 30
minutes, maintaining the stirring and cooling throughout. Hydrogen
chloride is steadily evolved. When the addition of the acetyl chloride is
complete, replace the ice-bath by a water-bath, and maintain the
temperature of the latter at 20-25° for 2 hours with constant stirring.
During this period hydrogen chloride continues to be liberally evolved,
and the product darkens considerably in colour. Now pour the product
cautiously into 500 ml. of dilute hydrochloric acid and ioo g. of chipped
ice in a separating-funnel, and shake the mixture thoroughly: this
operation removes the dark colour, and the toluene solution becomes
yellow. Run off the lower acid layer, and extract the toluene three
times with water. Finally dry the toluene solution over calcium chloride.
Fit a 75-100 ml. Claisen flask with a small dropping-funnel in the
main neck, and a water-condenser to the side-arm, and then run the
PREPARATIONS 291
filtered toluene solution slowly into the flask at such a rate that
the volume of solution entering is approximately the same as that of the
toluene (b.p. m°) distilling over. When the unchanged toluene has
thus been removed, replace the funnel by a capillary tube, and con-
tinue the distillation under reduced pressure by means of a water-
pump. The />-methylacetophenone is obtained as a colourless liquid,
b.p. 110-1120X1S mm -> leaving a dark residue in the flask. Yield
20-25 S- The ketone may require redistillation to obtain a sharply-
boiling fraction. It can be distilled at atmospheric pressure, and has
b.p. 220-224°/76o mm.
p-ETHYLTOLUENE. Required: p-Methylacetophenone,
1
S £•*> granulated zinc, 40 g.; mercuric chloride, 5 g.

To prepare the amalgamated zinc, place 40 g. of granulated


zinc in a 750 ml. flask, and clean the surface by first shaking
the zinc with a small quantity of acetone, then decanting off the
acetone and repeating the process with distilled water. Dissolve
5 g. of mercuric chloride in ioo ml. of distilled water con-
taining 5 ml. of concentrated hydrochloric acid, add the solution
to the zinc, and shake the mixture gently for about 5 minutes.
Decant the solution from the amalgamated zinc, and then pour
on to the latter 200 ml. of water and 200 ml. of concentrated
hydrochloric acid. Add 15 g. of p-methylacetophenone, fit
the flask to a reflux water-condenser, and boil the mixture for 6
hours: during the latter half of this period add 30 ml. of concen-
trated hydrochloric acid, ca. 5 ml. at a time, down the condenser.

Cool the mixture and pour the liquid reaction product into a
separating-funnel. Rinse out the flask (which may contain some
unchanged zinc) with ether, pour the latter into the funnel, and
extract the aqueous solution with the ether. Repeat the extrac-
tion with a second quantity of ether, unite the ether extracts,
wash them by extracting once with water, and then dry the
ethereal extract over sodium sulphate.

Filter the dried extract, and then distil off the ether from a
small flask, using the customary precautions: if the volume of
ether is large, fit a dropping-funnel to the flask so that the
ethereal extract can be run into the flask as the ether distils off
(cf. Fig. 23(fi), p. 45). When the ether has been removed,
replace the water-condenser by an air-condenser, and continue
the distillation. The p-cthyltolucne distils at 161-162° as a
colourless liquid. Yield, io g.
292 PRACTICAL ORGANIC CHEMISTRY
9,io-Dihydroanthracene-9,io-endo-a3-succinic
Anhydride. (The Diels-Alder Reaction.)
The Diels-Alder Reaction consists in the direct combination of a compound
containing a conjugated diene system with a reagent which possesses a double or
triple bond activated by suitable adjacent groups. Examples of such reagents are
maleic anhydride, />-benzoquinone, acraldehyde and acetylene dicarboxylic
esters. Combination always occurs at the 1,4 positions of the diene system:

O
,CH2
A
CH CH
Il Il
HC CH^CH

8
thus butadiene combines with />-benzoquinone as shown above; in this case a
second molecule of butadiene can similarly add on to the opposite side of the
p-benzoquinone ring.
The Diels-Alder Reaction usually occurs readily: it is of great value (a) for
diagnosing the presence of a conjugated diene grouping, (6) for synthetic
purposes in the preparation of cyclic systems.
In the following preparation, this reaction is exemplified by the union of
anthracene with maleic anhydride, to form 9,io-dihydroanthracene-9,io-£ndo-
a(3-succinic anhydride: note that as a result of this reaction both the outer rings
of the anthracene system become truly aromatic in character.

CH-CO

CH-CO
H > = O
CH-CO

CH-CO

Required: Anthracene, 2 g.; maleic anhydride, i g.


Add 2 g. of anthracene and i g. maleic anhydride to 25 ml.
of dry xylene, and boil the mixture under reflux: during the
early stages of the heating, keep the mixture gently shaken until a
clear solution is obtained, otherwise a portion of the reagents may
adhere to the base of the flask and darken because of local over-
heating. After boiling for 20 minutes, cool the solution, when
the addition product will rapidly crystallise. Filter at the pump,
and drain well. (Yield of crude material, which is almost pure,
ca. 2-7 g.) Recrystallise from about 50 ml. of xylene with the
addition if necessary of a small quantity of animal charcoal: filter
the solution through a small preheated funnel, as the solute
rapidly crystallises as the solution begins to cool. Place the recrys-
PREPARATIONS 293
tallised material in a vacuum desiccator, preferably over fresh
paraffin-wax shavings to absorb traces of xylene. The addition
product is obtained as colourless crystals, m.p. 256-258°. Yield
ca. 2 g.
2,4-Dimethylpyrrole-3,5-dicarboxylic Acid Diethyl Ester.
This synthesis of the pyrrole ring system, due to Knorr, consists in the con-
densation of an a-aminoketone with a i,3-diketone or the ester of a p-keto-acid.
ot-Aminoketones are unstable in the free state, readily undergoing self-condensa-
tion: consequently they must be prepared, by the reduction of an oc-nitroso (or
oximino) ketone, in the presence of the i,3-diketone or p-ketoester, to ensure
rapid interaction.
In the present preparation, ethyl acetoacetate is treated with sufficient nitrous
acid to convert half into the a-nitroso (or a-oximino) ester, which is reduced by
zinc and acetic acid to the a-amino ester (I). The latter then condenses with
CH3COCHC-NO)-COOC8H6 ^ CHSCOC(:NOH)-COOCSH6
I
CH 3 COCH(-NH 2 )-COOC 2 H 6 (I)
CH3-C-OH HC-COOC1H5 CH8-C C-COOC1H,
11 + 11 - II Il
C 1 H 6 OOC-C-NH 2 HO-C-CH 3 C 2 H 6 OOC-C C-CH 3
(D (ID (III) \ /
N
H
unchanged ethyl acetoacetate (II), both reagents being shown above in their
enol forms, to give the diethyl ester of 2,4-dimcthylpyrrole-3,5-dicarboxylic
acid (III).
The synthesis will therefore normally produce a z,4-substituted pyrrole,
with in addition an ester group or an acyl group at the 3-position, if a keto-ester
or a diketone respectively has been employed, and an ester group or an alkyl
(aryl) group at the 5-position, according to the nature of the amino-ketone.
Required: Ethyl acetoacetate, 20 g.; sodium nitrite, 5-4 g.;
zinc dust, n g.; glacial acetic acid, 60 ml.
Fit a three-necked 250 ml. flask with a central rubber-sleeved or
mercury-sealed stirrer, c/. Fig. 23(0), p. 45, where only two necks
are shown, and with a thermometer the bulb of which reaches as
near the bottom of the flask as the stirrer allows: the third neck
will carry at first a dropping-funnel and later a reflux condenser.
Place 20 g. (19*5 ml.) of ethyl acetoacetate and 45 ml. of glacial
acetic acid in the flask and by ice-water cooling adjust the
temperature of the stirred mixture to 5-7°: maintain this tem-
perature whilst adding a solution of 5-4 g. of sodium nitrite in
8 ml. of water slowly from the dropping-funnel during 15
minutes. Continue the stirring for 20-30 minutes, and then
294 PRACTICAL ORGANIC CHEMISTRY
remove the external cooling so that the mixture slowly attains
room temperature.
After 3 hours, replace the separating-funnel by a reflux
condenser, and the thermometer by a stopper. Add n g. of
zinc dust in small portions by rapid removal of the stopper at
such a rate that the liquid is first brought to the boil (usually
about 2 portions of 2 g. each) and is then maintained gently
boiling. Avoid too rapid addition of the zinc^ otherwise the
reaction will become too vigorous, and rapid immersion of the
flask in ice-water will be necessary to control the effervescence.
When the reaction is complete, heat the stirred mixture care-
fully under reflux over a Bunsen burner and asbestos gauze for
i hour: if the mixture becomes too thick for efficient stirring,
add up to 15 ml. of acetic acid. Now decant the hot mixture
into 500 ml. of vigorously-stirred ice-cold water: wash the
residual zinc thoroughly with glacial acetic acid (2 portions
each of 1-2 ml.), decanting the acid also into the stirred water.
The diethyl ester which is precipitated rapidly solidifies on
stirring. Filter it at the pump, wash with water (2 portions each
of about 20 ml.), and recrystallise from methylated spirit or from
95% ethanol. Yield of pale yellow crystals, 8-9 g.; m.p. 135-
137°.
1,2,3,4-Tetrahydro-carbazole. (The Fischer Indolisation
Reaction.)
The Fischer Indolisation Reaction occurs when the phenylhydrazone of a
suitable aldehyde or ketone undergoes cyclisation with loss of ammonia, under
the influence of various reagents, such as zinc chloride, ethanolic hydrogen
chloride, or acetic acid. For example, the phenylhydrazone of acetophenone
(P- 257) when heated with zinc chloride gives 2-phenylindole:
CH 3
C 6 H 5 NHNH 2 -f CH 3 COC 6 H 5 > C 6 H 6 NHNrC-C 6 H 6

(For the mechanism of this reaction, see Robinson and Robinson, J.C.S., 1918,
11
B* 639; 1924, 145, 827.) The reaction is of wide application: for example, the
use of methyl-phenyl-hydrazine, C 6 H 5 (CH 3 )X-NH 2 , in the above reaction
gives i-methyI-2-phenylindole, whereas pyruvic acid, CH 1 -CO-COOH, when
converted to its phenylhydrazone and then indolised, gives indole-2-carboxylic
PREPARATIONS 295
acid. The ease of cyclisation of various hydrazones varies greatly. Indole itself
cannot be prepared from acetaldehyde phenylhydrazone: on the other hand, the
phenylhydrazones of some saturated cyclic ketones undergo cyclisation very
readily even when boiled with acetic acid. This is illustrated in the following
preparation, in which cyclohexanone is converted into its phenylhydrazone, and
the latter, without isolation, is converted into 1,2,3,4-tetrahydrocarbazole by
boiling with acetic acid:
,CH2 CH2
H 2 C CH2 H2C CH2
C 6 H 5 NH-NH 2 + I I —j, i I _
OC CH2 C 6 H 5 NH-NiC CH 2
X
CH2 \{i2

Required: Cyclohexanone, 9 ml.; phenylhydrazine, 8 ml.


Dissolve 8-8 g. (9-0 ml.) of cyclohexanone in 50 ml. of
glacial acetic acid, add 8 ml. of phenylhydrazine, and boil the
solution under reflux for 5 minutes. Cool the solution, when the
tetrahydrocarbazole will crystallise out. Filter at the pump,
drain well, and recrystallise either from aqueous ethanol or
(better) from aqueous acetic acid. The recrystallisation should be
performed rapidly, for the tetrahydrocarbazole undergoes atmo-
spheric oxidation in hot solutions: after recrystallisation, the
compound should be dried in a vacuum desiccator and not in an
oven. Repeated recrystallisation should be avoided. The tetra-
hydrocarbazole, after thorough drying, is obtained as colourless
crystals, m.p. 118°: yield of recrystallised material, n g.
If cold saturated ethanolic solutions of the recrystallised
tetrahydrocarbazole and of picric acid are mixed and stirred, the
chocolate-brown picrate of the carbazole slowly crystallises.
After it has been filtered off at the pump, washed with a small
quantity of ethanol, and dried, it has m.p. 145-146°.

Diethyl Collidine-3,5-dicarboxylate.
(The Hantzsch Reaction.)
This reaction consists of the condensation of two molecular equivalents of a
i,3-diketone (or a (3-keto-ester) with one equivalent of an aldehyde and one of
ammonia. Thus the interaction of ethyl acetoacetate and acetaldehyde and
ammonia affords the i,4-dihydro-pyridine derivative (I), which when boiled
with dilute nitric acid readily undergoes dehydrogenation and "aromatisation"
to give the diethyl ester of collidine (or 2,4,6-trimethyl-pyridine-3,5-dicarboxylic
acid (U)). For the initial condensation the solid aldehyde-ammonia can con-
veniently be used in place of the separate reagents.
To obtain the free acid, the ester is hydrolysed by ethanolic potash to the
dipotassium salt, which is converted into the insoluble silver salt. A hot aqueous
296 PRACTICAL ORGANIC CHEMISTRY
CH3 CH3
CH /CH
EtOOC-CH, 6 H2C-COOEt
fc EtOOC-C
T
CH3-CO
I
OC-CH3
—- Il l
CH3-Cx /C CH3
—>•
NH33 N
(D H
CH3
EtOOC -/\-COOEt
H3C-1( J-CH3
(U) N
suspension of this salt when treated with hydrogen sulphide gives the dicar-
boxylic acid.

Required: Ethyl acetoacetate, 32 g. (32 ml.); acetaldehyde-


ammonia, 10 g. (Note. The aldehyde-ammonia should preferably
be fresh material: the quantity should be increased to 15 g. if an
old sample, which has formed brown sticky lumps, is employed.)
Gently warm a mixture of 32 g. (32 ml.) of ethyl acetoacetate
and 10 g. of aldehyde-ammonia in a 400 ml. beaker by direct
heating on a gauze, stirring the mixture carefully with a thermo-
meter. As soon as the reaction starts, remove the heating, and
replace it when the reaction slackens, but do not allow the
temperature of the mixture to exceed 100-110°: the reaction is
rapidly completed. Add to the mixture about twice its volume
of 2Ar-hydrochloric acid, and stir the mass until the deposit
either becomes solid or forms a thick paste, according to the
quality of the aldehyde-ammonia employed. Decant the aqueous
acid layer, repeat the extraction of the deposit with more acid,
and again decant the acid, or filter off the deposit if it is solid.
Transfer the deposit to a conical flask and recrystallise it twice
from ethanol (or methylated spirit) diluted with an equal
volume of water. The i,4-dihydro-collidine-3,5-dicarboxylic
diethyl ester (I) is obtained as colourless crystals, m.p. 130-131°.
Yield: 12-5 g.
For dehydrogenation, add this ester to dilute nitric acid
(20 ml. of the concentrated acid diluted with 40 ml. of water)
and boil the mixture under reflux for about 5 minutes, during
which the ester gently effervesces and finally gives a clear
solution. Cool this solution in ice-water, make alkaline with
aqueous sodium carbonate solution and extract twice with ether
(50 ml. for each extraction). Dry the extract with sodium
sulphate, filter, and then distil using a small distilling-flask
PREPARATIONS 297
(Fig. 4i(A) and (B), p. 65) into which the ethereal extract is al-
lowed to run from a dropping-funnel at approximately the rate
at which the solvent is distilling. When the ether has been
removed, fit a capillary tube and thermometer, and continue the
distillation at water-pump pressure. The diethyl ester of colli-
dine-3,5-dicarboxylic acid (II) distils as a pale golden oil, b.p.
i76-i78°/i4 mm. Yield, 5 g. from 6 g. of the ester (I).
Collidine-3,$-dicarboxylic acid. Boil a mixture of 5 g. of the ester (II) and
50 ml. of 15% ethanolic potash under reflux for 30 minutes. The dipotassium
salt crystallises during the boiling and during the subsequent cooling. Filter off
the potassium salt at the pump and wash it with a small quantity of ethanol.
Dilute the filtrate with about an equal volume of ether to precipitate a further
small crop of the salt. Yield of combined crops: 4-5 g. from 5 g. of the ester (I).
To obtain the free acid, add a solution of 2 g. of the potassium salt in 15 ml.
of hot water slowly with stirring to 50 ml. of boiling 6% aqueous silver nitrate
solution, and then gently boil the complete mixture for a few minutes to coagu-
late the precipitated silver salt. Filter the hot mixture at the pump, wash the
silver salt with water and drain well. Transfer the silver salt to a large boiling-
tube, add 30 ml. of water, and stir the mixture to give a uniform suspension.
Heat to boiling and pass a stream of hydrogen sulphide through the mixture
until all the silver has formed the heavy sulphide, leaving a clear solution above.
Heat again almost to boiling, and filter the supernatant solution through a pre-
heated funnel: boil the residual silver sulphide with 10-15 ml. of water, filter
and evaporate the united filtrates to about 25 ml. The solution, when cooled
and stirred, slowly deposits the colourless crystalline dicarboxylic acid, which can
be recrystallised from ethanol containing 20% of water. Yield, i g.
The use of lead nitrate in place of silver nitrate is to be avoided, for the pre-
cipitated lead sulphide occludes most of the free acid.

Quinoline. C 9 H 7 N. (Skraup's Synthesis.)


When a mixture of aniline, nitrobenzene, glycerol and concentrated sul-
phuric acid is heated, a vigorous reaction occurs with the formation of quino-
line. It is probable that the sulphuric acid first dehydrates the glycerol giving
acrolein or acraldehyde (A), which then condenses at its double bond with the
amino group of the aniline to give acrolein-aniline (B). The latter in its enol
CH 2 (OH)-CH(OH)CH 2 (OH) — 2 H 2 O = CH2:CH CHO (A)
C 6 H 5 NH 2 + CH 8 :CH CHO = C 6 H 6 NHCH 2 CH 2 CHO (B)
form (C) then undergoes ring-closure to give the unstable intermediate com-
pound (D), which is at once oxidised by the nitrobenzene to quinoline (E).
JHO)CH ^ CH ^ CH
^* • _u_r\ Y if \^i i _2H

(D)
The nitrobenzene is thus itself reduced to aniline, which can then react as before.
298 PRACTICAL ORGANIC CHEMISTRY
When the crude reaction product is made alkaline and steam-distilled, a
mixture of quinoline and some unchanged aniline passes over. Pure quinoline
can be isolated from this mixture by one of the following methods:
(1) The mixed bases are dissolved in dilute hydrochloric acid and sodium
nitrite solution added. The aniline is thus diazotised and, if the mixture is
subsequently boiled, converted into phenol. The solution is then made alka-
line and steam-distilled, the quinoline passing over, while the phenol remains
behind in the alkaline solution.
(2) The mixed bases are boiled with an acetic acid-acetic anhydride mixture
to convert the aniline into acetanilide. The product is poured into water,
when the acetanilide crystallises out while the quinoline remains in solution as
quinoline acetate. The acetanilide is filtered off, and the filtrate made alkaline
and steam-distilled.
(3) The mixed amines are dissolved in hydrochloric acid and zinc chloride
solution added. The quinoline chlorozincate,* (C 9 H 7 N) 2 ,H 1 ZnCl 4 , crystallises
out, being almost insoluble in water, while the aniline chlorozincate remains in
solution. The quinoline chlorozincate is then filtered off and decomposed by
alkalis, and the liberated quinoline extracted with ether or steam-distilled.
Of the above methods for separating the amines, number (3) is the best.
Required: Aniline, 24 ml.; nitrobenzene, 13 ml.; anhydrous
glycerol, 62 ml.; sulphuric acid, 36 ml.; zinc chloride, 23 g.
The reaction is carried out in a 2-litre long-necked round-bottomed
flask, to which is fitted an efficient reflux water-condenser, capable of
condensing a sudden rush of vapour without choking. For this
purpose, a long bulb-condenser, similar to that shown in Fig. 3(A)
(p. 9) is best, but the inner tube must be of wide bore (at least 12
mm.). Alternatively, an air-condenser of wide bore may be used, and
a short double-surface water-condenser fitted to its top. A steam-
distillation fitting for the flask should also be prepared in advance,
so that the crude product can subsequently be steam-distilled directly
from the flask. The glycerol used in the preparation must be anhy-
drous, and should therefore be dehydrated by the method described on
p. 113.
Place 24 ml. (24-5 g.) of aniline, 13 ml. (15-5 g.) of nitro-
benzene,! and 62 ml. (75 g.) of the anhydrous glycerol in
the ftask and mix thoroughly. (If the glycerol is still warm from
the dehydration, cool the mixture in water.) Now add slowly
36 ml. (66 g.) of concentrated sulphuric acid, shaking the
mixture thoroughly during the addition. The mixture at first
* These chlorozincates must not be confused with the non-ionic compounds
which quinoline and aniline bases give with neutral zinc chloride: the latter
have the formulae [(C 9 H 7 N) 2 ZnCl 2 ] and [(C 4 H 7 N) 8 ZnCl 2 ] respectively, and
both are only slightly soluble in water.
t The initial reaction proceeds more smoothly if 37 g. of dry arsenic acid
are used in place of the nitrobenzene for oxidation purposes. The yields when
arsenic acid is used are, however, uncertain and often low.
PREPARATIONS 299
becomes semi-solid owing to the separation of aniline sulphate,
but later becomes mobile as the temperature rises during the
further addition of the acid. Now add some fragments of un-
glazed porcelain, fit the reflux condenser to the flask, and support
the latter on a gauze-covered tripod, preferably in a fume-
cupboard; clamp the condenser so that it is inclined at about
60° to the horizontal, as "choking" is less likely in this position
than in a vertical position. Now heat the flask cautiously with a
Bunsen flame: immediately the reaction starts and bubbles of
vapour form in the liquid, turn out the gas. (It is advisable to
have a duster soaked in cold water at hand: if, when the reaction
starts, the duster is wrapped around the upper part of the body of
the flask, the risk of the condenser choking becomes negligible.)
When the vigorous reaction subsides, replace the gauze by a
sand-bath and boil the mixture gently for 3 hours. By this time
the reaction is complete, and no unchanged nitrobenzene should
remain. Then add about an equal volume of water, cool, and add
concentrated sodium hydroxide solution until the mixture is
definitely alkaline to litmus-paper. Steam-distil the product until
the crude quinoline has been driven completely over and the
distillate leaving the condenser is no longer turbid (usually about
700 ml.). Extract the quinoline with ether and then either distil
off the ether taking the usual precautions (p. 163), or, if the
amount of ether used is small, evaporate the ether in an open
basin on a water-bath, the gas being turned out immediately
before the basin is placed in position. (Chloroform may be used
instead of ether, but its complete removal from the quinoline
requires distillation.). Dissolve the crude residual quinoline in
200 ml. of dilute hydrochloric acid (i vol. concentrated acid to
4 vols. water), warm the solution to about 60°, and add a solution
of 23 g. of zinc chloride in 40 ml. of dilute hydrochloric acid. The
quinoline chlorozincate soon starts to crystallise. Cool the well-
stirred mixture thoroughly in ice-water and when crystallisation is
complete, filter at the pump, wash well with dilute hydrochloric
acid, and drain.
Transfer the quinoline chlorozincate to a beaker, add a small
quantity of water, and then add 10% sodium hydroxide solution
until the initial precipitate of zinc hydroxide completely redis-
solves, and the free quinoline separates. Transfer the mixture to
a separating-funnel, wash out the beaker with ether, adding the
washings also to the solution in the funnel, and then extract the
quinoline twice with ether. Dry the united ethereal extracts by
adding an ample quantity of powdered potassium hydroxide and
3°° PRACTICAL ORGANIC CHEMISTRY
allowing the mixture to stand overnight. Then filter the ethereal
solution, wash the residual potash with more ether and then distil
off the ether from a small (75 ml.) flask with the usual precautions
(Fig. 64, p. 16^). Then replace the water-condenser by an air-
condenser and distil the quinoline. Collect the fraction of b.p.
234-237°. Yield, 18 g.
Quinoline is a colourless liquid, having b.p. 236° and d, 1-095.
It has an odour similar to, but fainter than," that of pyridine:
unlike pyridine, it is almost insoluble in water.

Quinaldine. C10H9N. (The Doebner-Miller Synthesis.)


Quinaldine (or 2-methylquinoline) can be prepared by the Doebner-Miller
Synthesis, which in some respects is closely similar to the Skraup Synthesis
(p. 297) but has some significant differences.
When a mixture of aniline, hydrochloric acid and acetaldehyde is heated
(in the absence of an oxidising agent), a vigorous reaction occurs with the pro-
duction of quinaldine. In these circumstances, the main reactions are un-
doubtedly, (i) the acetaldehyde undergoes the aldol condensation, and the
2CH3-CHO -> CH 3 -CH(OH)-CH 2 -CHO -> CH 3 -CHiCH-CHO (D
product then loses water to give crotonaldehyde (I); (ii) the aniline then under-
goes a i ,4-addition to the crotonaldehyde to give the intermediate compound

(HO)CH

H-CH, CH-CH 3

(III) (IV)

(II), -which by cyclic dehydration forms i,2-dihydro-i-methylquinoline (III).


These stages are closely similar to those of the Skraup Synthesis which produce
the compound (D) (p. 297). The dihydro derivative (III) readily loses hydrogen
to give quinaldine (IV).
Since no oxidising agent is present in the reaction-mixture, this dehydro-
genation must involve the reduction of other components of the mixture. The
reduced products are mainly A'-ethylanilinc, C 6 H 5 NH-C 2 H 5 , and A T -;;-butyl-
aniline, C«H 6 NH-(CH 2 ) 3 -CH 3 , together with a small quantity of 6-ethyl-
quinaldine. It is reasonably certain that a small proportion of the aniline must
combine with the acetaldehyde and with the crotonaldehyde to give the corres-
ponding Schiff's bases (V) and (VI) respectively: these compounds are then
C 6 H 6 -NiCH-CH 3 (V) C 6 H 6 -N:CH-CH:CH-CH 8 (VI)
reduced by the dihydro derivative (III), which by losing its i,2-hydrogen atoms
attains the increased stability of the aromatic system (IV).
PREPARATIONS 301
The small quantity of 6-ethylquinaldine probably arises by the acetaldehyde
attacking the />-position of the aniline to give the ^)-CH 3 CH(OH)-CeH 4 -NH-
group, either in the aniline itself or in one of the intermediates, followed by
both cyclisation and reduction.
The secondary amines present in the crude quinaldine are most effectively
removed by acetylation.
It is convenient to replace the volatile free acetaldehyde by paraldehyde,
which by dissociation in the reaction-mixture generates acetaldehyde in situ.

Required: Aniline, 30 ml. (30-5 g.); paraldehyde, 45 ml.


(45 £•)'» concentrated hydrochloric acid, 60 ml.
The reaction is best carried out in the apparatus used in the
preparation of quinoline, a 1500 ml. flask being fitted with a
wide-bore air-condenser carrying in turn a water-condenser:
a still-head to fit the flask for subsequent steam-distillation
should be assembled in advance.
Add 60 ml. of concentrated hydrochloric acid with shaking
to 30 ml. of aniline in the flask, cool the mixture to about 50°,
and then add 45 ml. of paraldehyde and some fragments of un-
glazed porcelain; assemble the apparatus without delay in a fume-
cupboard with the condenser inclined at an angle of about 60°.
It is best now to proceed as in the Skraup Synthesis (p. 297)
and warm the mixture over an asbestos-covered gauze with a
Bunsen flame until the reaction starts, and have at hand a duster
soaked in cold water so that when the reaction starts, the heating
can be at once removed and the duster wrapped round the
shoulders of the flask to aid condensation.
When the reaction has subsided, boil the reaction-mixture
under reflux for 2 hours: then make it alkaline with sodium
hydroxide solution, and distil it in steam until oily drops no
longer come over in the aqueous distillate (1^-2 litres). Extract
the distillate thoroughly with ether (ca. 150 ml.), and dry the
ethereal extract over powdered sodium hydroxide. Filter the dry
extract through a fluted filter-paper moistened with ether into a
200 ml. flask. Fit the flask with a distillation-head, or a "knee-
tube", and distil off the ether. Now replace the distillation-head
by a reflux water-condenser, add 10 ml. of acetic anhydride, and
boil the mixture under reflux for 10-15 minutes.
The pure quinaldine can now be isolated by either of the
following methods, (a) Transfer the acetylated mixture to a
Claisen flask (preferably having a short fractionating column
below the side-arm) and distil the mixture slowly at water-pump
pressure by heating the flask in an oil or silicone bath. The
first fraction, of b.p. ca. S°°/1S mm -i contains acetic acid and
302 PRACTICAL ORGANIC CHEMISTRY
anhydride. The next fraction is a golden liquid, b.p. i2O-i3o°/i5
mm., of almost pure quinaldine, weighing 18 g. If this fraction
has been distilled slowly, the distillation will stop when this frac-
tion is complete. Stronger heating then causes a rapid rise of the
boiling-point as the by-products begin to distil, and should be
avoided. The quinaldine should be redistilled from a clean flask,
and obtained as a colourless hygroscopic liquid, 120-123°/15 mm.,
weighing 15-16 g. (b) The second method requires far more
time. Cool the acetylated liquid, make it alkaline with saturated
aqueous sodium carbonate, replace the condenser by a steam-
distillation head, and again steam-distil until all the quinaldine
has passed over. Extract the distillate with ether, dry the extract
as before, and distil the filtered extract, taking off the ether at
atmospheric pressure and the quinaldine at water-pump pressure.
Collect the quinaldine, of b.p. I20-i22°/i5 mm. Yield, 15 g.
Quinaldine Methiodide. Boil a mixture of 3 ml. of quinaldine, 2 ml. of
methanol and 3 ml. of methyl iodide gently under reflux for i \ hours,
during which the methiodide will start to crystallise. Cool the mixture
thoroughly in ice-water, filter off the methiodide and recrystallise it
from ethanol: pale yellow crystals, m.p. 194°.
Dissolve a small quantity of the methiodide in cold water and add it with
shaking to an excess of cold saturated aqueous sodium picrate solution. A
yellow double salt* of quinaldine methopicrate and sodium picnite,
[C 1 1 H 1 2 X]C 6 H 2 X 3 O^NaCeH 3 N 3 O 7 ,
m.p. 218-220°, is rapidly precipitated, but when filtered off and recrystallised
from water gives the simple quinaldine methopicrate, [C 11 H 12 N]C 6 H 2 N 3 O 7 ,
m.p. 141°.
p'Dimethylaminostyryl-quinoline. The methyl group in 2-methylquinoline
(quinaldine) and in 4-methylquinoline (lepidine) has comparatively high
reactivity, whereas that in 3-methylquinoline has low reactivity. The reactivity
of the methyl group in quinaldine is shown by its ready condensation with
aldehydes: in general, this condensation with the quinaldine base occurs most
readily in an acid medium, whereas that with quinaldine methiodide (and other
quaternary salts) best in a basic medium, e.g., in the presence of a small quantity
of piperidine.
Mix i g. of quinaldine and i g. of powdered p-dimethylaminobenzal-
dehyde, add 2-3 drops of io% ethanolic zinc chloride solution, and
heat under reflux in an oil-bath at 150° for i hour. Cool the product
in ice-water, and recrystallise it from ethanol. />-Dimethylaminostyryl-
quinoline (I) separates as bright yellow crystals, m.p. 177-178°.

* For examples of other similar methopicrntes uniting \\ith picric acid or


sodium picrate to give "double picrates" of various stabilities, see V. (i. M a n n
and F. C. Baker, J. Client. Sm-., n » 6 i , 3X45.
PREPARATIONS 3°3
Dissolve ca. 0-2 g. of product (I) in cold ethanol, and add with shaking 1-2
drops of dilute sulphuric acid. A deep purple coloration appears at once. This
shows that salt formation has occurred on the quinoline nitrogen atom to form
the cation (!!A), which will form a resonance hybrid with the quinonoid form
(!!B). [Note that the forms (!!A) and (IIfi) differ only in electron position, an